rs3808185

Positions:

• chr7-117574035-T-C
• chr7-117574035-T-G

Variant summary

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

The NM_000492.4(CFTR):​c.1585-13704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,964 control chromosomes in the GnomAD database, including 3,123 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 0.19 (3123 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1585-13704T>C		intron_variant		ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1585-13704T>C		intron_variant		1	NM_000492.4	ENSP00000003084	P2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28062 AN: 151846 Hom.: 3113 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.185 AC: 28117 AN: 151964 Hom.: 3123 Cov.: 32 AF XY: 0.194 AC XY: 14424 AN XY: 74254

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.155

Alfa AF: 0.120 Hom.: 1739

Bravo AF: 0.189

Asia WGS AF: 0.409 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.68

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: rs3808185; hg19: chr7-117214089;