Variant 1-86430858-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006536.7(CLCA2):c.476-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,609,854 control chromosomes in the GnomAD database, including 102,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8802 hom., cov: 32)

Exomes 𝑓: 0.36 ( 93319 hom. )

Consequence

CLCA2
NM_006536.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007262

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.945

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCA2	NM_006536.7 linkuse as main transcript	c.476-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370565.5	NP_006527.1
CLCA2	XM_011542448.4 linkuse as main transcript	c.476-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_011540750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA2	ENST00000370565.5 linkuse as main transcript	c.476-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006536.7	ENSP00000359596	P1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51178

AN:

151896

Hom.:

8797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.356

AC:

88497

AN:

248838

Hom.:

16156

AF XY:

0.359

AC XY:

48268

AN XY:

134454

show subpopulations

Gnomad AFR exome

AF:

0.306

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.498

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.356

AC:

518579

AN:

1457840

Hom.:

93319

Cov.:

AF XY:

0.357

AC XY:

259049

AN XY:

725222

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.337

AC:

51207

AN:

152014

Hom.:

8802

Cov.:

AF XY:

0.336

AC XY:

24953

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.340

Hom.:

20832

Bravo

AF:

0.332

Asia WGS

AF:

0.439

AC:

1529

AN:

3478

EpiCase

AF:

0.348

EpiControl

AF:

0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000073

dbscSNV1_RF

Benign

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over