chr7-117579781-C-T

Position:

• chr7-117579781-C-T

Variant summary

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

The NM_000492.4(CFTR):​c.1585-7958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 150,028 control chromosomes in the GnomAD database, including 2,802 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 0.18 (2802 hom., cov: 31)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFTR	NM_000492.4	c.1585-7958C>T		intron_variant		ENST00000003084.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11	c.1585-7958C>T		intron_variant		1	NM_000492.4	P2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26588 AN: 149940 Hom.: 2792 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.178 AC: 26638 AN: 150028 Hom.: 2802 Cov.: 31 AF XY: 0.188 AC XY: 13722 AN XY: 73122

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.150

Alfa AF: 0.132 Hom.: 308

Bravo AF: 0.180

Asia WGS AF: 0.398 AC: 1369 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.63
DANN	Benign	0.46

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: rs1469486; hg19: chr7-117219835;