rs213965

Variant names:

• chr7-117589483-T-A
• rs213965
• NM_000492.4:c.1680-870T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-117589483-T-A
• chr7-117589483-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.1680-870T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,808 control chromosomes in the GnomAD database, including 25,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.54 (25193 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.811
• Publications: 12 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-117589483-T-A is Benign according to our data. Variant chr7-117589483-T-A is described in ClinVar as Benign. ClinVar VariationId is 53332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1680-870T>A		intron_variant	Intron 12 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1680-870T>A		intron_variant	Intron 12 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82513 AN: 151690 Hom.: 25125 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82640 AN: 151808 Hom.: 25193 Cov.: 32 AF XY: 0.546 AC XY: 40465 AN XY: 74156

African (AFR) AF: 0.835 AC: 34635 AN: 41496

American (AMR) AF: 0.512 AC: 7803 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 958 AN: 3464

East Asian (EAS) AF: 0.422 AC: 2181 AN: 5166

South Asian (SAS) AF: 0.481 AC: 2317 AN: 4818

European-Finnish (FIN) AF: 0.518 AC: 5456 AN: 10542

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27830 AN: 67760

Other (OTH) AF: 0.502 AC: 1058 AN: 2106

Alfa AF: 0.380 Hom.: 1333

Bravo AF: 0.555

Asia WGS AF: 0.524 AC: 1809 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystic fibrosis Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 15, 2017

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. -

Sep 16, 2020

Natera, Inc.

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 -

not provided Benign:2

Apr 28, 2022

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 26, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 06, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1680-870T>A in intron 12 of CFTR: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. The A allele is the major allele but the frequency of the T allele is hig h enough to rule out a role in disease (A = 94.3%; 166/176 and T = 5.7% , 10/1 76 Yoruban chromosomes, 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/proje cts/SNP; dbSNP rs213965). -

CFTR-related disorder Benign:1

Nov 19, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.38
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs213965; hg19: chr7-117229537;