rs2834600

chr21-34713804-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CLIC6	NM_053277.3	c.1900-2517C>T		intron_variant		ENST00000349499.3
CLIC6	NM_001317009.2	c.1954-2517C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC6	ENST00000349499.3	c.1900-2517C>T		intron_variant		1	NM_053277.3	P2
CLIC6	ENST00000360731.7	c.1954-2517C>T		intron_variant		1		A2

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

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.102

Alfa AF: 0.123 Hom.: 1717

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

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

Other links and lift over

dbSNP: rs2834600; hg19: chr21-36086102;