rs10281281

Positions:

• chr7-117564408-A-G

Variant summary

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

The ENST00000003084.11(CFTR):​c.1584+4753A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,204 control chromosomes in the GnomAD database, including 2,944 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 (2944 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFTR ENST00000003084.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

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-AS1 (HGNC:40144): (CFTR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1584+4753A>G		intron_variant		ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1	n.161+108T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1584+4753A>G		intron_variant		1	NM_000492.4	ENSP00000003084	P2
CFTR-AS1	ENST00000441019.1	n.161+108T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16384 AN: 152086 Hom.: 2942 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0870

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 108 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.108 AC: 16408 AN: 152204 Hom.: 2944 Cov.: 32 AF XY: 0.103 AC XY: 7677 AN XY: 74428

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00188

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.0468 Hom.: 425

Bravo AF: 0.124

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.83

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: rs10281281; hg19: chr7-117204462;