rs4656100

Positions:

• chr1-86452261-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CLCA2	NM_006536.7	c.2156-1108T>C		intron_variant		ENST00000370565.5	NP_006527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA2	ENST00000370565.5	c.2156-1108T>C		intron_variant		1	NM_006536.7	ENSP00000359596	P1
CLCA2	ENST00000498802.1	n.507-1108T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.582

Alfa AF: 0.550 Hom.: 14545

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

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: rs4656100; hg19: chr1-86917944; COSMIC: COSV65286608;