Variant chr1-86560314-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_012128.4(CLCA4):c.405del(p.Asp136ThrfsTer102) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,614,010 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

CLCA4
NM_012128.4 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.966

Variant links:

Genes affected

CLCA4 (HGNC:2018): (chloride channel accessory 4) The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Alternative splicing results in multiple transcript variants, only one of which is thought to be protein coding. [provided by RefSeq, Dec 2008]

CLCA4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-86560314-CT-C is Benign according to our data. Variant chr1-86560314-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 775566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLCA4	NM_012128.4 linkuse as main transcript	c.405del	p.Asp136ThrfsTer102	frameshift_variant	3/14	ENST00000370563.3	NP_036260.2
CLCA4	XM_011541015.3 linkuse as main transcript	c.252del	p.Asp85ThrfsTer102	frameshift_variant	3/14		XP_011539317.1
CLCA4	NR_024602.2 linkuse as main transcript	n.447del		non_coding_transcript_exon_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA4	ENST00000370563.3 linkuse as main transcript	c.405del	p.Asp136ThrfsTer102	frameshift_variant	3/14	1	NM_012128.4	ENSP00000359594	P1	Q14CN2-1

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

276

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000429

AC:

107

AN:

249358

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.00601

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

252

AN:

1461744

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00612

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152266

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00628

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.00214

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over