rs2834600

Variant names:

• chr21-34713804-C-T
• rs2834600
• NM_053277.3:c.1900-2517C>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.1900-2517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,198 control chromosomes in the GnomAD database, including 829 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 0.091 (829 hom., cov: 32)
• Consequence: CLIC6 NM_053277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3	c.1900-2517C>T		intron_variant	Intron 5 of 5	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2	c.1954-2517C>T		intron_variant	Intron 6 of 6		NP_001303938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC6	ENST00000349499.3	c.1900-2517C>T		intron_variant	Intron 5 of 5	1	NM_053277.3	ENSP00000290332.4
CLIC6	ENST00000360731.7	c.1954-2517C>T		intron_variant	Intron 6 of 6	1		ENSP00000353959.3

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13893 AN: 152080 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0912 AC: 13888 AN: 152198 Hom.: 829 Cov.: 32 AF XY: 0.0885 AC XY: 6586 AN XY: 74408

African (AFR) AF: 0.0268 AC: 1113 AN: 41536

American (AMR) AF: 0.0976 AC: 1492 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4822

European-Finnish (FIN) AF: 0.111 AC: 1171 AN: 10578

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9175 AN: 67998

Other (OTH) AF: 0.102 AC: 215 AN: 2108

Alfa AF: 0.120 Hom.: 2089

Bravo AF: 0.0886

Asia WGS AF: 0.0140 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.21
PhyloP100		-1.1
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: rs2834600; hg19: chr21-36086102;