rs2180762

Positions:

• chr1-86473707-G-A
• chr1-86473707-G-C

Variant summary

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

The NM_001285.4(CLCA1):​c.304-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,556,322 control chromosomes in the GnomAD database, including 719,747 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 0.92 (65001 hom., cov: 33)
  • Exomes 𝑓: 0.97 (654746 hom.)
• Consequence: CLCA1 NM_001285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCA1	NM_001285.4	c.304-22G>A		intron_variant		ENST00000394711.2	NP_001276.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA1	ENST00000394711.2	c.304-22G>A		intron_variant		1	NM_001285.4	ENSP00000378200	P1
CLCA1	ENST00000234701.7	c.304-22G>A		intron_variant		1		ENSP00000234701	P1

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140229 AN: 152152 Hom.: 64963 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.929

GnomAD3 exomes AF: 0.951 AC: 210143 AN: 220932 Hom.: 100181 AF XY: 0.953 AC XY: 114191 AN XY: 119766

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.975

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 0.986

Gnomad SAS exome AF: 0.957

Gnomad FIN exome AF: 0.882

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.961

GnomAD4 exome AF: 0.965 AC: 1355301 AN: 1404052 Hom.: 654746 Cov.: 30 AF XY: 0.965 AC XY: 669070 AN XY: 693116

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.973

Gnomad4 ASJ exome AF: 0.983

Gnomad4 EAS exome AF: 0.991

Gnomad4 SAS exome AF: 0.957

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.960

GnomAD4 genome AF: 0.922 AC: 140323 AN: 152270 Hom.: 65001 Cov.: 33 AF XY: 0.919 AC XY: 68399 AN XY: 74452

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.928

Alfa AF: 0.955 Hom.: 18196

Bravo AF: 0.923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.59

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: rs2180762; hg19: chr1-86939390;