NM_001285.4:c.2436T>C

Variant names:

• chr1-86499736-T-C
• rs1882753
• NM_001285.4:c.2436T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001285.4(CLCA1):​c.2436T>C​(p.Thr812Thr) 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
• Publications: 20 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]

ENSG00000299069 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA1	NM_001285.4	MANE Select	c.2436T>C	p.Thr812Thr	synonymous	Exon 14 of 14	NP_001276.3	A8K7I4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA1	ENST00000394711.2	TSL:1 MANE Select	c.2436T>C	p.Thr812Thr	synonymous	Exon 14 of 14	ENSP00000378200.1	A8K7I4
	CLCA1	ENST00000234701.7	TSL:1	c.2436T>C	p.Thr812Thr	synonymous	Exon 15 of 15	ENSP00000234701.3	A8K7I4
	CLCA1	ENST00000957889.1		c.2433T>C	p.Thr811Thr	synonymous	Exon 14 of 14	ENSP00000627948.1

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

GnomAD2 exomes AF: 0.297 AC: 74506 AN: 250978 AF XY: 0.300

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 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

African (AFR) AF: 0.269 AC: 8972 AN: 33318

American (AMR) AF: 0.259 AC: 11576 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6318 AN: 26098

East Asian (EAS) AF: 0.510 AC: 20208 AN: 39650

South Asian (SAS) AF: 0.398 AC: 34238 AN: 86118

European-Finnish (FIN) AF: 0.251 AC: 13397 AN: 53270

Middle Eastern (MID) AF: 0.214 AC: 1235 AN: 5762

European-Non Finnish (NFE) AF: 0.262 AC: 290323 AN: 1106180

Other (OTH) AF: 0.288 AC: 17325 AN: 60192

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

African (AFR) AF: 0.269 AC: 11152 AN: 41508

American (AMR) AF: 0.240 AC: 3665 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2743 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4828

European-Finnish (FIN) AF: 0.242 AC: 2565 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18118 AN: 68002

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.267 Hom.: 17075

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.93
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: rs1882753; hg19: chr1-86965419; COSMIC: COSV52327934;