1-86499736-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001285.4(CLCA1):​c.2436T>G​(p.Thr812Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.929 with no splicing effect.

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>G	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>G	p.Thr812Thr	synonymous	Exon 14 of 14	ENSP00000378200.1	A8K7I4
	CLCA1	ENST00000234701.7	TSL:1	c.2436T>G	p.Thr812Thr	synonymous	Exon 15 of 15	ENSP00000234701.3	A8K7I4
	CLCA1	ENST00000957889.1		c.2433T>G	p.Thr811Thr	synonymous	Exon 14 of 14	ENSP00000627948.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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;