7-117595001-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000492.4(CFTR):c.2562T>G(p.Thr854Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,611,676 control chromosomes in the GnomAD database, including 101,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15267 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86541 hom. )

Consequence

CFTR
NM_000492.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 0.278

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-117595001-T-G is Benign according to our data. Variant chr7-117595001-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 43577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117595001-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.278 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.2562T>G	p.Thr854Thr	synonymous_variant	Exon 15 of 27	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.2562T>G	p.Thr854Thr	synonymous_variant	Exon 15 of 27	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64588

AN:

151756

Hom.:

15229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.383

AC:

96181

AN:

251152

Hom.:

19751

AF XY:

0.374

AC XY:

50715

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.337

AC:

491244

AN:

1459802

Hom.:

86541

Cov.:

AF XY:

0.336

AC XY:

244394

AN XY:

726342

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.407

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.415

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.426

AC:

64673

AN:

151874

Hom.:

15267

Cov.:

AF XY:

0.429

AC XY:

31828

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.321

Hom.:

6097

Bravo

AF:

0.433

Asia WGS

AF:

0.466

AC:

1618

AN:

3468

EpiCase

AF:

0.296

EpiControl

AF:

0.290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Jan 19, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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

- -

Dec 27, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cystic fibrosis

Benign:5

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2023

Payam Genetics Center, General Welfare Department of North Khorasan Province

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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 -

CFTR-related disorder

Benign:2

Mar 28, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary pancreatitis

Benign:1

Dec 09, 2019

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

-0.82

CADD

Benign

4.7

DANN

Benign

0.35

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