rs10487372

Positions:

• chr7-117560845-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.1584+1190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,860 control chromosomes in the GnomAD database, including 1,275 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 0.12 (1275 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFTR	NM_000492.4	c.1584+1190C>T		intron_variant		ENST00000003084.11
CFTR-AS1	NR_149084.1	n.162-53G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11	c.1584+1190C>T		intron_variant		1	NM_000492.4	P2
CFTR-AS1	ENST00000441019.1	n.162-53G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18784 AN: 151740 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.124 AC: 18816 AN: 151860 Hom.: 1275 Cov.: 32 AF XY: 0.127 AC XY: 9390 AN XY: 74200

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.129

Alfa AF: 0.113 Hom.: 1287

Bravo AF: 0.116

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.38

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: rs10487372; hg19: chr7-117200899;