Genetic Variant CLIC6:p.Gly177Gly (chr21-34669919-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_053277.3(CLIC6):c.531C>T(p.Gly177Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,182,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G177G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

CLIC6
NM_053277.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.96

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-2.96 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC6	NM_053277.3	MANE Select	c.531C>T	p.Gly177Gly	synonymous	Exon 1 of 6	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.531C>T	p.Gly177Gly	synonymous	Exon 1 of 7	NP_001303938.1	Q96NY7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIC6	ENST00000349499.3	TSL:1 MANE Select	c.531C>T	p.Gly177Gly	synonymous	Exon 1 of 6	ENSP00000290332.4	Q96NY7-2
CLIC6	ENST00000360731.7	TSL:1	c.531C>T	p.Gly177Gly	synonymous	Exon 1 of 7	ENSP00000353959.3	Q96NY7-1
CLIC6	ENST00000954659.1		c.531C>T	p.Gly177Gly	synonymous	Exon 1 of 8	ENSP00000624718.1

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

93432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

9848

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000367

AC:

AN:

1089032

Hom.:

Cov.:

AF XY:

0.00000384

AC XY:

AN XY:

520990

show subpopulations

African (AFR)

AF:

0.0000934

AC:

AN:

21420

American (AMR)

AF:

0.00

AC:

AN:

8510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12910

East Asian (EAS)

AF:

0.00

AC:

AN:

20550

South Asian (SAS)

AF:

0.00

AC:

AN:

38490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2806

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920252

Other (OTH)

AF:

0.0000470

AC:

AN:

42540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000856

AC:

AN:

93432

Hom.:

Cov.:

AF XY:

0.0000884

AC XY:

AN XY:

45234

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

23570

American (AMR)

AF:

0.00

AC:

AN:

9448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2500

East Asian (EAS)

AF:

0.00

AC:

AN:

3284

South Asian (SAS)

AF:

0.00

AC:

AN:

2838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

45070

Other (OTH)

AF:

0.00

AC:

AN:

1250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.8

(source)

DANN

Benign

0.85

PhyloP100

-3.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over