chr7-117479869-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000546407.1(CFTR):n.166+4061G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 593,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

CFTR
ENST00000546407.1 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:3

Conservation

PhyloP100: 1.54

Publications

1 publications found

Variant links:

Genes affected

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR Gene-Disease associations (from GenCC):

cystic fibrosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
congenital bilateral absence of vas deferens
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary chronic pancreatitis
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CFTR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 7-117479869-G-T is Benign according to our data. Variant chr7-117479869-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 51031.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000546407.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.-226G>T		upstream_gene	N/A	NP_000483.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFTR	ENST00000546407.1	TSL:1	n.166+4061G>T	intron	N/A
CFTR	ENST00000673785.1		c.-406+14038G>T	intron	N/A	ENSP00000501235.1
CFTR	ENST00000446805.2	TSL:4	c.-191+175G>T	intron	N/A	ENSP00000417012.1

Frequencies

GnomAD3 genomes

AF:

0.00387

AC:

587

AN:

151620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00242

GnomAD4 exome

AF:

0.000620

AC:

274

AN:

441970

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

125

AN XY:

233892

show subpopulations

African (AFR)

AF:

0.0155

AC:

193

AN:

12436

American (AMR)

AF:

0.00138

AC:

AN:

19600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13540

East Asian (EAS)

AF:

0.00

AC:

AN:

30432

South Asian (SAS)

AF:

0.000131

AC:

AN:

45852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28390

Middle Eastern (MID)

AF:

0.000515

AC:

AN:

1940

European-Non Finnish (NFE)

AF:

0.00000756

AC:

AN:

264382

Other (OTH)

AF:

0.00177

AC:

AN:

25398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00391

AC:

593

AN:

151738

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

266

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.0133

AC:

551

AN:

41364

American (AMR)

AF:

0.00237

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67914

Other (OTH)

AF:

0.00239

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00627

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:4Benign:1

Jul 02, 2025

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Published functional studies demonstrate decreased Sp1 and USF DNA-binding and decreased transcriptional activity in one study that utilized a core promoter construct, but the associated transcriptional activity was not significantly different from wild type in a second study that utilized a full-length promoter construct (PMID: 17678620, 21948798); Identified in individuals with cystic fibrosis in published literature, but in whom a second CFTR variant was either not detected or not specified (PMID: 10204861, 31665830, 18832460); Describes a nucleotide substitution 226 basepairs upstream of the ATG translational start site in the 5' untranslated region (UTR); Also known as c.-94G>T; Located in a regulatory region; in the absence of functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 12939925, 26656651, 11168023, 31665830, 18832460, 21948798, 10204861, 37313453, 17678620)

Apr 04, 2024

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The CFTR c.-266G>T variant has been reported in the published literature in individuals with cystic fibrosis (CF) (PMIDs: 31665830 (2020), 18832460 (2008), 11168023 (2001), 10204861 (1999)). Functional studies indicate this variant may impact promoter activity but further evidence is needed to understand the global impact of this variant on disease (PMIDs: 17678620 (2007), 21948798 (2012)). The frequency of this variant in the general population, 0.014 (117/8656 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.

Jun 15, 2018

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 02, 2021

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cystic fibrosis

Benign:2

Aug 12, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Apr 26, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.5

PromoterAI

0.071

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over