rs3765986

chr1-86448489-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.1984+711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,214 control chromosomes in the GnomAD database, including 4,961 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 0.25 (4961 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: CLCA2 NM_006536.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCA2	NM_006536.7	c.1984+711T>C		intron_variant		ENST00000370565.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCA2	ENST00000370565.5	c.1984+711T>C		intron_variant		1	NM_006536.7	P1
CLCA2	ENST00000498802.1	n.335+21T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37274 AN: 152086 Hom.: 4958 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.245 AC: 37310 AN: 152206 Hom.: 4961 Cov.: 32 AF XY: 0.246 AC XY: 18334 AN XY: 74414

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.221

Alfa AF: 0.264 Hom.: 1082

Bravo AF: 0.236

Asia WGS AF: 0.327 AC: 1136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.1
Dann	Benign	0.68

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: rs3765986; hg19: chr1-86914172;