rs980574

chr7-117511774-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000492.4(CFTR):c.273+2632A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,024 control chromosomes in the GnomAD database, including 26,587 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 0.56 (26587 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFTR	NM_000492.4	c.273+2632A>C		intron_variant		ENST00000003084.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11	c.273+2632A>C		intron_variant		1	NM_000492.4	P2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84666 AN: 151906 Hom.: 26521 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.558 AC: 84792 AN: 152024 Hom.: 26587 Cov.: 32 AF XY: 0.561 AC XY: 41652 AN XY: 74272

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.510

Alfa AF: 0.521 Hom.: 2840

Bravo AF: 0.565

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.4
Dann	Benign	0.63

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

Other links and lift over

dbSNP: rs980574; hg19: chr7-117151828;