rs10487367

chr7-117441426-G-T

Variant summary

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

The ENST00000673785.1(CFTR):c.-490-24321G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,542 control chromosomes in the GnomAD database, including 2,267 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 0.17 (2267 hom., cov: 32)
• Consequence: CFTR ENST00000673785.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 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.-490-24321G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25321 AN: 151432 Hom.: 2271 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.167 AC: 25322 AN: 151542 Hom.: 2267 Cov.: 32 AF XY: 0.166 AC XY: 12293 AN XY: 74010

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0892

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.161

Alfa AF: 0.183 Hom.: 449

Bravo AF: 0.157

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	11
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10487367; hg19: chr7-117081480;