rs2791498

Positions:

• chr1-86491941-G-T

Variant summary

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

The NM_001285.4(CLCA1):​c.1464+570G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 150,810 control chromosomes in the GnomAD database, including 13,526 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 0.41 (13526 hom., cov: 33)
• Consequence: CLCA1 NM_001285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

Genes affected

CLCA1 (HGNC:2015): (chloride channel accessory 1) This gene encodes a member of the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same region on chromosome 1p31-p22 and share a high degree of homology in size, sequence, and predicted structure, but differ significantly in their tissue distributions. The encoded protein is expressed as a precursor protein that is processed into two cell-surface-associated subunits, although the site at which the precursor is cleaved has not been precisely determined. The encoded protein may be involved in mediating calcium-activated chloride conductance in the intestine. [provided by RefSeq, Jul 2008]

LOC124904210 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCA1	NM_001285.4	c.1464+570G>T		intron_variant		ENST00000394711.2
LOC124904210	XR_007066206.1	n.226-11133C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCA1	ENST00000394711.2	c.1464+570G>T		intron_variant		1	NM_001285.4	P1
CLCA1	ENST00000234701.7	c.1464+570G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62519 AN: 150692 Hom.: 13524 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.415 AC: 62544 AN: 150810 Hom.: 13526 Cov.: 33 AF XY: 0.411 AC XY: 30284 AN XY: 73596

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.420

Alfa AF: 0.432 Hom.: 2450

Bravo AF: 0.408

Asia WGS AF: 0.274 AC: 951 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	0.74
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2791498; hg19: chr1-86957624;