1-86499736-T-C

Position:

• chr1-86499736-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001285.4(CLCA1):​c.2436T>C​(p.Thr812=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,607,498 control chromosomes in the GnomAD database, including 64,776 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 0.28 (6061 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58715 hom.)
• Consequence: CLCA1 NM_001285.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.929 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCA1	NM_001285.4	c.2436T>C	p.Thr812=	synonymous_variant	14/14	ENST00000394711.2
LOC124904210	XR_007066206.1	n.226-18928A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCA1	ENST00000394711.2	c.2436T>C	p.Thr812=	synonymous_variant	14/14	1	NM_001285.4	P1
CLCA1	ENST00000234701.7	c.2436T>C	p.Thr812=	synonymous_variant	15/15	1		P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41897 AN: 152074 Hom.: 6061 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.268

GnomAD3 exomes AF: 0.297 AC: 74506 AN: 250978 Hom.: 12101 AF XY: 0.300 AC XY: 40710 AN XY: 135722

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.398

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.277 AC: 403592 AN: 1455306 Hom.: 58715 Cov.: 30 AF XY: 0.280 AC XY: 203152 AN XY: 724342

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.275 AC: 41917 AN: 152192 Hom.: 6061 Cov.: 33 AF XY: 0.280 AC XY: 20816 AN XY: 74410

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.265

Alfa AF: 0.268 Hom.: 11362

Bravo AF: 0.273

Asia WGS AF: 0.460 AC: 1602 AN: 3478

EpiCase AF: 0.256

EpiControl AF: 0.252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.62

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: rs1882753; hg19: chr1-86965419; COSMIC: COSV52327934;