Variant 21-34669926-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_053277.3(CLIC6):c.538G>T(p.Val180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,313,850 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 21 hom., cov: 30)

Exomes 𝑓: 0.00074 ( 12 hom. )

Consequence

CLIC6
NM_053277.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.375

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026577115).

BP6

Variant 21-34669926-G-T is Benign according to our data. Variant chr21-34669926-G-T is described in ClinVar as [Benign]. Clinvar id is 710983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00724 (1091/150588) while in subpopulation AFR AF= 0.025 (1023/40880). AF 95% confidence interval is 0.0238. There are 21 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC6	NM_053277.3 linkuse as main transcript	c.538G>T	p.Val180Leu	missense_variant	1/6	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2 linkuse as main transcript	c.538G>T	p.Val180Leu	missense_variant	1/7		NP_001303938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC6	ENST00000349499.3 linkuse as main transcript	c.538G>T	p.Val180Leu	missense_variant	1/6	1	NM_053277.3	ENSP00000290332	P2	Q96NY7-2
CLIC6	ENST00000360731.7 linkuse as main transcript	c.538G>T	p.Val180Leu	missense_variant	1/7	1		ENSP00000353959	A2	Q96NY7-1

Frequencies

GnomAD3 genomes

AF:

0.00724

AC:

1089

AN:

150466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00408

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:

0.0000148

Gnomad OTH

AF:

0.00242

GnomAD3 exomes

AF:

0.000159

AC:

AN:

18914

Hom.:

AF XY:

0.00

AC XY:

AN XY:

10150

show subpopulations

Gnomad AFR exome

AF:

0.00196

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000736

AC:

856

AN:

1163262

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

367

AN XY:

562176

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000365

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000187

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00724

AC:

1091

AN:

150588

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

513

AN XY:

73610

show subpopulations

Gnomad4 AFR

AF:

0.0250

Gnomad4 AMR

AF:

0.00407

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00124

Hom.:

ExAC

AF:

0.000788

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.2

DANN

Benign

0.85

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.0030

Sift

Benign

0.079

T;T

Sift4G

Uncertain

0.037

D;D

Polyphen

0.17

B;B

Vest4

0.11

MutPred

0.13

Gain of glycosylation at S179 (P = 0.1443);Gain of glycosylation at S179 (P = 0.1443);

MVP

0.27

MPC

2.0

ClinPred

0.0048

GERP RS

-0.26

Varity_R

0.046

gMVP

0.046

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