rs39317

Positions:

• chr7-117326250-G-A

Variant summary

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

The ENST00000673785.1(CFTR):​c.-491+25220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,904 control chromosomes in the GnomAD database, including 13,988 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 0.42 (13988 hom., cov: 32)
• Consequence: CFTR ENST00000673785.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000673785.1	c.-491+25220G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64290 AN: 151786 Hom.: 13945 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.424 AC: 64395 AN: 151904 Hom.: 13988 Cov.: 32 AF XY: 0.429 AC XY: 31858 AN XY: 74230

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.414

Alfa AF: 0.387 Hom.: 6442

Bravo AF: 0.426

Asia WGS AF: 0.527 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs39317; hg19: chr7-116966304;