rs34010645

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBS1BS2

The NM_000492.4(CFTR):c.164+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,049,952 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).

Frequency

Genomes: 𝑓 0.0054 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 6 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

Clinical Significance

Uncertain significance reviewed by expert panel U:2B:8

Conservation

PhyloP100: 0.421

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-117504391-A-G is Benign according to our data. Variant chr7-117504391-A-G is described in ClinVar as [Uncertain_significance]. Clinvar id is 235283.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=6, Uncertain_significance=2}. Variant chr7-117504391-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00544 (828/152320) while in subpopulation AFR AF= 0.0186 (773/41582). AF 95% confidence interval is 0.0175. There are 7 homozygotes in gnomad4. There are 409 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.164+28A>G		intron_variant	Intron 2 of 26	ENST00000003084.11	NP_000483.3	P13569-1A0A024R730

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.164+28A>G		intron_variant	Intron 2 of 26	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

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:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00142

AC:

335

AN:

235408

Hom.:

AF XY:

0.000943

AC XY:

120

AN XY:

127272

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.000805

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000607

AC:

545

AN:

897632

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

229

AN XY:

470326

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.000898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000270

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000367

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00544

AC:

828

AN:

152320

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00619

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Benign:8

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Sep 28, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CFTR: BS1, BS2 -

Nov 01, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 21, 2021

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cystic fibrosis

Uncertain:1Benign:2

Aug 31, 2018

CFTR2

Significance: Uncertain significance

Review Status: reviewed by expert panel

Collection Method: research

- -

Oct 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 21, 2022

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. -

not specified

Benign:1

Jan 17, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary pancreatitis

Benign:1

Apr 28, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.9

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over