rs214164

Variant names:

• chr7-117652642-G-A
• rs214164
• NM_000492.4:c.3874-200G>A

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.3874-200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,930 control chromosomes in the GnomAD database, including 2,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.19 (2847 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.55
• Publications: 4 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=-0.93).
• BP6: Variant 7-117652642-G-A is Benign according to our data. Variant chr7-117652642-G-A is described in ClinVar as Benign. ClinVar VariationId is 818097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.3874-200G>A		intron_variant	Intron 23 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.3874-200G>A		intron_variant	Intron 23 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28390 AN: 151810 Hom.: 2844 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.187 AC: 28410 AN: 151930 Hom.: 2847 Cov.: 32 AF XY: 0.187 AC XY: 13863 AN XY: 74232

African (AFR) AF: 0.189 AC: 7817 AN: 41428

American (AMR) AF: 0.158 AC: 2412 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5178

South Asian (SAS) AF: 0.188 AC: 908 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2434 AN: 10506

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13755 AN: 67962

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.207 Hom.: 523

Bravo AF: 0.178

Asia WGS AF: 0.106 AC: 367 AN: 3440

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cystic fibrosis Benign: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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0050
DANN	Benign	0.35
PhyloP100		-2.6
PromoterAI		-0.0074	Neutral
Mutation Taster		=97/3	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: rs214164; hg19: chr7-117292696;