rs2180762

Variant names:

• chr1-86473707-G-A
• rs2180762
• NM_001285.4:c.304-22G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLCA1	NM_001285.4	c.304-22G>A		intron_variant	Intron 2 of 13	ENST00000394711.2	NP_001276.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA1	ENST00000394711.2	c.304-22G>A		intron_variant	Intron 2 of 13	1	NM_001285.4	ENSP00000378200.1
CLCA1	ENST00000234701.7	c.304-22G>A		intron_variant	Intron 3 of 14	1		ENSP00000234701.3

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

GnomAD2 exomes AF: 0.951 AC: 210143 AN: 220932 AF XY: 0.953

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 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

African (AFR) AF: 0.813 AC: 25317 AN: 31126

American (AMR) AF: 0.973 AC: 33932 AN: 34890

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 23024 AN: 23424

East Asian (EAS) AF: 0.991 AC: 38672 AN: 39032

South Asian (SAS) AF: 0.957 AC: 74706 AN: 78046

European-Finnish (FIN) AF: 0.888 AC: 46127 AN: 51922

Middle Eastern (MID) AF: 0.958 AC: 5282 AN: 5514

European-Non Finnish (NFE) AF: 0.973 AC: 1052873 AN: 1082414

Other (OTH) AF: 0.960 AC: 55368 AN: 57684

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

African (AFR) AF: 0.820 AC: 34035 AN: 41512

American (AMR) AF: 0.958 AC: 14672 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3401 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5121 AN: 5190

South Asian (SAS) AF: 0.959 AC: 4634 AN: 4834

European-Finnish (FIN) AF: 0.885 AC: 9388 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65929 AN: 68034

Other (OTH) AF: 0.928 AC: 1959 AN: 2112

Alfa AF: 0.953 Hom.: 18476

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
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2180762; hg19: chr1-86939390;