rs213968

Variant names:

• chr7-117589939-C-T
• rs213968
• NM_000492.4:c.1680-414C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000492.4(CFTR):​c.1680-414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,798 control chromosomes in the GnomAD database, including 25,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (25213 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.1680-414C>T		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.1680-414C>T		intron_variant	Intron 12 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82562 AN: 151680 Hom.: 25145 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.404

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: 0.545 AC: 82689 AN: 151798 Hom.: 25213 Cov.: 32 AF XY: 0.546 AC XY: 40497 AN XY: 74156

African (AFR) AF: 0.835 AC: 34669 AN: 41530

American (AMR) AF: 0.511 AC: 7799 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3466

East Asian (EAS) AF: 0.423 AC: 2182 AN: 5158

South Asian (SAS) AF: 0.482 AC: 2316 AN: 4802

European-Finnish (FIN) AF: 0.518 AC: 5462 AN: 10544

Middle Eastern (MID) AF: 0.383 AC: 111 AN: 290

European-Non Finnish (NFE) AF: 0.411 AC: 27842 AN: 67732

Other (OTH) AF: 0.502 AC: 1060 AN: 2110

Alfa AF: 0.509 Hom.: 2710

Bravo AF: 0.555

Asia WGS AF: 0.523 AC: 1817 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.39
PhyloP100		-1.0
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: rs213968; hg19: chr7-117229993; COSMIC: COSV50052803; COSMIC: COSV50052803;