rs2834601

Variant names:

• chr21-34716756-C-T
• rs2834601
• NM_053277.3:c.*274C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053277.3(CLIC6):​c.*274C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 214,862 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (443 hom., cov: 32)
  • Exomes 𝑓: 0.059 (136 hom.)
• Consequence: CLIC6 NM_053277.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3	c.*274C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2	c.*274C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001303938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC6	ENST00000349499.3	c.*274C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_053277.3	ENSP00000290332.4
CLIC6	ENST00000360731.7	c.*274C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000353959.3

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10893 AN: 151632 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0859

GnomAD4 exome AF: 0.0592 AC: 3738 AN: 63110 Hom.: 136 Cov.: 0 AF XY: 0.0579 AC XY: 1870 AN XY: 32288

African (AFR) AF: 0.0775 AC: 137 AN: 1768

American (AMR) AF: 0.0384 AC: 93 AN: 2424

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 285 AN: 2432

East Asian (EAS) AF: 0.0587 AC: 250 AN: 4260

South Asian (SAS) AF: 0.0334 AC: 114 AN: 3412

European-Finnish (FIN) AF: 0.0434 AC: 140 AN: 3226

Middle Eastern (MID) AF: 0.124 AC: 41 AN: 330

European-Non Finnish (NFE) AF: 0.0576 AC: 2373 AN: 41168

Other (OTH) AF: 0.0746 AC: 305 AN: 4090

GnomAD4 genome AF: 0.0718 AC: 10897 AN: 151752 Hom.: 443 Cov.: 32 AF XY: 0.0710 AC XY: 5261 AN XY: 74148

African (AFR) AF: 0.0861 AC: 3560 AN: 41354

American (AMR) AF: 0.0589 AC: 898 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3466

East Asian (EAS) AF: 0.112 AC: 578 AN: 5148

South Asian (SAS) AF: 0.0485 AC: 232 AN: 4788

European-Finnish (FIN) AF: 0.0605 AC: 634 AN: 10486

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.0636 AC: 4320 AN: 67958

Other (OTH) AF: 0.0878 AC: 185 AN: 2106

Alfa AF: 0.0689 Hom.: 865

Bravo AF: 0.0729

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.57
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs2834601; hg19: chr21-36089054;