7-117548628-GTTTTTT-GTTTTTTTT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000492.4(CFTR):c.1210-7_1210-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 142,512 control chromosomes in the GnomAD database, including 184 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 184 hom., cov: 31)

Exomes 𝑓: 0.030 ( 422 hom. )

Failed GnomAD Quality Control

Consequence

CFTR
NM_000492.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 0.565

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:

CFTR-AS1 (HGNC:40144): (CFTR antisense RNA 1)

CFTR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-117548628-G-GTT is Benign according to our data. Variant chr7-117548628-G-GTT is described in ClinVar as [Likely_benign]. Clinvar id is 161188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.1210-7_1210-6dupTT		splice_region_variant, intron_variant	Intron 9 of 26	ENST00000003084.11	NP_000483.3	P13569-1A0A024R730
CFTR-AS1	NR_149084.1 link	n.222-6091_222-6090dupAA		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.1210-13_1210-12insTT		intron_variant	Intron 9 of 26	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6243

AN:

142412

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0664

Gnomad AMI

AF:

0.0101

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00275

Gnomad SAS

AF:

0.0345

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.0311

Gnomad OTH

AF:

0.0324

GnomAD3 exomes

AF:

0.0333

AC:

6825

AN:

205052

Hom.:

AF XY:

0.0330

AC XY:

3693

AN XY:

111880

show subpopulations

Gnomad AFR exome

AF:

0.0700

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00153

Gnomad SAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0305

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0299

AC:

42111

AN:

1406430

Hom.:

422

Cov.:

AF XY:

0.0295

AC XY:

20617

AN XY:

699778

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.00584

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0278

GnomAD4 genome

AF:

0.0439

AC:

6260

AN:

142512

Hom.:

184

Cov.:

AF XY:

0.0473

AC XY:

3286

AN XY:

69466

show subpopulations

Gnomad4 AFR

AF:

0.0664

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00276

Gnomad4 SAS

AF:

0.0343

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0311

Gnomad4 OTH

AF:

0.0367

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 16, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cystic fibrosis

Benign:3Other:1

Jan 29, 2018

CFTR-France

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

the variant does not result in CFTR-RD neither -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

The severity of lung disease in individuals heterozygous or homozygous for p.Arg117His depends on the presence of a variation in the poly T tract of intron 9, c.1210-12T[5_9] [Massie et al 2001]. Individuals with a CF-causing variant plus the 5T variant in cis with p.Arg117His usually develop the lung disease of CF, but those individuals with p.Arg117His and the 7T variant or the 9T variant have a highly variable phenotype that can range from no symptoms to mild lung disease [Kiesewetter et al 1993, Chmiel et al 1999]. -

Dec 18, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 29, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 06, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Intact protein function observed by in vitro/ex vivo assays;Intronic alteration with no splicing impact by rt-pcr analysis or other splicing assay;Other strong data -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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