chr21-34677070-C-T

Variant names:

• chr21-34677070-C-T
• rs1009925
• NM_053277.3:c.1374+6308C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053277.3(CLIC6):​c.1374+6308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 152,286 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.

• Frequency: Genomes: 𝑓 0.0014 (0 hom., cov: 32)
• Consequence: CLIC6 NM_053277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.1374+6308C>T		intron	N/A	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.1374+6308C>T		intron	N/A	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.1374+6308C>T		intron	N/A	ENSP00000290332.4	Q96NY7-2
	CLIC6	ENST00000360731.7	TSL:1	c.1374+6308C>T		intron	N/A	ENSP00000353959.3	Q96NY7-1
	CLIC6	ENST00000954659.1		c.1374+6308C>T		intron	N/A	ENSP00000624718.1

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.000956

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

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85 AN XY: 74450

African (AFR) AF: 0.000650 AC: 27 AN: 41568

American (AMR) AF: 0.00216 AC: 33 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00210 AC: 143 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00202 Hom.: 0

Bravo AF: 0.00162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
PhyloP100		-3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1009925; hg19: chr21-36049369;