rs17547853

Variant names:

• chr7-117586850-G-A
• rs17547853
• NM_000492.4:c.1585-889G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-117586850-G-A
• chr7-117586850-G-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.1585-889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,858 control chromosomes in the GnomAD database, including 1,185 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 0.11 (1185 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1585-889G>A		intron_variant	Intron 11 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1585-889G>A		intron_variant	Intron 11 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16629 AN: 151740 Hom.: 1186 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.109 AC: 16621 AN: 151858 Hom.: 1185 Cov.: 32 AF XY: 0.109 AC XY: 8115 AN XY: 74194

African (AFR) AF: 0.0326 AC: 1353 AN: 41454

American (AMR) AF: 0.118 AC: 1798 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3464

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5158

South Asian (SAS) AF: 0.0630 AC: 302 AN: 4796

European-Finnish (FIN) AF: 0.196 AC: 2061 AN: 10504

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10498 AN: 67908

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0905 Hom.: 184

Bravo AF: 0.0988

Asia WGS AF: 0.0280 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.66
PhyloP100		-0.094
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: rs17547853; hg19: chr7-117226904;