rs761426163

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000492.4(CFTR):c.744-9_744-6delGATT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,535,716 control chromosomes in the GnomAD database, including 38,096 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4348 hom., cov: 25)

Exomes 𝑓: 0.21 ( 33748 hom. )

Consequence

CFTR
NM_000492.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.82

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.

BP6

Variant 7-117536514-AGATT-A is Benign according to our data. Variant chr7-117536514-AGATT-A is described in ClinVar as [Benign]. Clinvar id is 43579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign]. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.744-9_744-6delGATT		splice_region_variant, intron_variant	Intron 6 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.744-33_744-30delGATT		intron_variant	Intron 6 of 26	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35190

AN:

151540

Hom.:

4333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.270

AC:

44068

AN:

163440

Hom.:

6756

AF XY:

0.267

AC XY:

23220

AN XY:

86906

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.415

Gnomad SAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.212

AC:

292985

AN:

1384058

Hom.:

33748

AF XY:

0.215

AC XY:

147376

AN XY:

684806

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.232

AC:

35245

AN:

151658

Hom.:

4348

Cov.:

AF XY:

0.242

AC XY:

17941

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.225

Bravo

AF:

0.232

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 20, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cystic fibrosis

Benign:2

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 -

Nov 19, 2014

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 provided

Benign:2

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CFTR-related disorder

Benign:1

May 15, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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