Variant 1-86571145-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_012128.4(CLCA4):c.1251C>T(p.Asn417Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,612,828 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 19 hom. )

Consequence

CLCA4
NM_012128.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

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:

CLCA4 (HGNC:):

CLCA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-86571145-C-T is Benign according to our data. Variant chr1-86571145-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638912.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCA4	NM_012128.4 linkuse as main transcript	c.1251C>T	p.Asn417Asn	synonymous_variant	8/14	ENST00000370563.3	NP_036260.2	Q14CN2-1
CLCA4	XM_011541015.3 linkuse as main transcript	c.1098C>T	p.Asn366Asn	synonymous_variant	8/14		XP_011539317.1
CLCA4	NR_024602.2 linkuse as main transcript	n.1184C>T		non_coding_transcript_exon_variant	7/13
CLCA4-AS1	NR_135837.1 linkuse as main transcript	n.*36G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLCA4	ENST00000370563.3 linkuse as main transcript	c.1251C>T	p.Asn417Asn	synonymous_variant	8/14	1	NM_012128.4	ENSP00000359594.3	Q14CN2-1
CLCA4	ENST00000496322.1 linkuse as main transcript	n.30C>T		non_coding_transcript_exon_variant	1/2	3
CLCA4-AS1	ENST00000699483.1 linkuse as main transcript	n.1547G>A		non_coding_transcript_exon_variant	5/5
CLCA4-AS1	ENST00000456587.1 linkuse as main transcript	n.*36G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00122

AC:

303

AN:

249030

Hom.:

AF XY:

0.00125

AC XY:

169

AN XY:

135098

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000754

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00173

AC:

2524

AN:

1460664

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1267

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152164

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00108

EpiCase

AF:

0.00153

EpiControl

AF:

0.00202

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

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

CLCA4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.20

DANN

Benign

0.55

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