chr1-86452261-T-C

Variant names:

• chr1-86452261-T-C
• rs4656100
• NM_006536.7:c.2156-1108T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006536.7(CLCA2):​c.2156-1108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 146,974 control chromosomes in the GnomAD database, including 23,438 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 0.56 (23438 hom., cov: 22)
• Consequence: CLCA2 NM_006536.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 5 publications found

Genes affected

CLCA2 (HGNC:2016): (chloride channel accessory 2) This gene encodes a member of the calcium-activated chloride channel regulator (CLCR) family of proteins. Members of this family regulate the transport of chloride across the plasma membrane. The encoded protein is autoproteolytically processed to generate N- and C- terminal fragments. Expression of this gene is upregulated by the tumor suppressor protein p53 in response to DNA damage. In breast cancer, expression of this gene is downregulated and the encoded protein may inhibit migration and invasion while promoting mesenchymal-to-epithelial transition in cancer cell lines. [provided by RefSeq, Sep 2016]

CLCA2 Gene-Disease associations (from GenCC):

• heart conduction disease

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCA2	NM_006536.7	c.2156-1108T>C		intron_variant	Intron 12 of 13	ENST00000370565.5	NP_006527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA2	ENST00000370565.5	c.2156-1108T>C		intron_variant	Intron 12 of 13	1	NM_006536.7	ENSP00000359596.4
CLCA2	ENST00000498802.1	n.507-1108T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 82346 AN: 146870 Hom.: 23405 Cov.: 22

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.664

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 82436 AN: 146974 Hom.: 23438 Cov.: 22 AF XY: 0.565 AC XY: 40234 AN XY: 71268

African (AFR) AF: 0.558 AC: 22124 AN: 39638

American (AMR) AF: 0.510 AC: 7412 AN: 14530

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1877 AN: 3454

East Asian (EAS) AF: 0.550 AC: 2703 AN: 4916

South Asian (SAS) AF: 0.680 AC: 3153 AN: 4634

European-Finnish (FIN) AF: 0.654 AC: 6091 AN: 9314

Middle Eastern (MID) AF: 0.657 AC: 184 AN: 280

European-Non Finnish (NFE) AF: 0.552 AC: 37160 AN: 67276

Other (OTH) AF: 0.582 AC: 1182 AN: 2030

Alfa AF: 0.551 Hom.: 22375

Bravo AF: 0.554

Asia WGS AF: 0.661 AC: 2299 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-0.59
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: rs4656100; hg19: chr1-86917944; COSMIC: COSV65286608;