chr21-34669919-C-G

Variant names:

• chr21-34669919-C-G
• rs752208168
• NM_053277.3:c.531C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_053277.3(CLIC6):​c.531C>G​(p.Gly177Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLIC6 NM_053277.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.96
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 21-34669919-C-G is Benign according to our data. Variant chr21-34669919-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 715385.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>G	p.Gly177Gly	synonymous	Exon 1 of 6	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.531C>G	p.Gly177Gly	synonymous	Exon 1 of 7	NP_001303938.1	Q96NY7-1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 112 AN: 92894 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00120

Gnomad EAS AF: 0.00184

Gnomad SAS AF: 0.00212

Gnomad FIN AF: 0.00353

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000806

GnomAD2 exomes AF: 0.00173 AC: 17 AN: 9848 AF XY: 0.00148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00143

Gnomad FIN exome AF: 0.00336

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000259 AC: 282 AN: 1088250 Hom.: 0 Cov.: 65 AF XY: 0.000279 AC XY: 145 AN XY: 520576

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000934 AC: 2 AN: 21416

American (AMR) AF: 0.00307 AC: 26 AN: 8466

Ashkenazi Jewish (ASJ) AF: 0.000466 AC: 6 AN: 12888

East Asian (EAS) AF: 0.0000973 AC: 2 AN: 20548

South Asian (SAS) AF: 0.00209 AC: 80 AN: 38306

European-Finnish (FIN) AF: 0.000650 AC: 14 AN: 21522

Middle Eastern (MID) AF: 0.000713 AC: 2 AN: 2806

European-Non Finnish (NFE) AF: 0.000158 AC: 145 AN: 919796

Other (OTH) AF: 0.000118 AC: 5 AN: 42502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00124 AC: 115 AN: 92920 Hom.: 0 Cov.: 26 AF XY: 0.00138 AC XY: 62 AN XY: 44984

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00166 AC: 39 AN: 23502

American (AMR) AF: 0.000852 AC: 8 AN: 9386

Ashkenazi Jewish (ASJ) AF: 0.00120 AC: 3 AN: 2494

East Asian (EAS) AF: 0.00185 AC: 6 AN: 3250

South Asian (SAS) AF: 0.00214 AC: 6 AN: 2802

European-Finnish (FIN) AF: 0.00353 AC: 17 AN: 4814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 94

European-Non Finnish (NFE) AF: 0.000735 AC: 33 AN: 44874

Other (OTH) AF: 0.000801 AC: 1 AN: 1248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00128 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs752208168; hg19: chr21-36042218; COSMIC: COSV62448417;