Variant chr21-34669928-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_053277.3(CLIC6):c.540A>G(p.Val180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000704 in 1,150,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLIC6
NM_053277.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.165

Variant links:

Genes affected

CLIC6 (HGNC:2065): (chloride intracellular channel 6) This gene encodes a member of the chloride intracellular channel family of proteins. The gene is part of a large triplicated region found on chromosomes 1, 6, and 21. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2015]

CLIC6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 21-34669928-A-G is Benign according to our data. Variant chr21-34669928-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 734248.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.165 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC6	NM_053277.3 linkuse as main transcript	c.540A>G	p.Val180=	synonymous_variant	1/6	ENST00000349499.3
CLIC6	NM_001317009.2 linkuse as main transcript	c.540A>G	p.Val180=	synonymous_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC6	ENST00000349499.3 linkuse as main transcript	c.540A>G	p.Val180=	synonymous_variant	1/6	1	NM_053277.3	P2	Q96NY7-2
CLIC6	ENST00000360731.7 linkuse as main transcript	c.540A>G	p.Val180=	synonymous_variant	1/7	1		A2	Q96NY7-1

Frequencies

GnomAD3 genomes

AF:

0.000124

AC:

AN:

137494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000289

Gnomad ASJ

AF:

0.00298

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000310

Gnomad OTH

AF:

0.000535

GnomAD3 exomes

AF:

0.000115

AC:

AN:

17434

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

9460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00862

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000704

AC:

AN:

1150126

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

555386

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.00320

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000241

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000124

AC:

AN:

137594

Hom.:

Cov.:

AF XY:

0.0000897

AC XY:

AN XY:

66878

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000289

Gnomad4 ASJ

AF:

0.00298

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000310

Gnomad4 OTH

AF:

0.000529

Alfa

AF:

0.000253

Hom.:

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

Invitae

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.3

DANN

Benign

0.49

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