rs373588470

Variant names:

• chr6-31730957-C-G
• rs373588470
• NM_001288.6:c.611G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31730957-C-G
• chr6-31730957-C-T
• chr6-31730957-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288.6(CLIC1):​c.611G>C​(p.Arg204Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CLIC1 NM_001288.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

CLIC1 (HGNC:2062): (chloride intracellular channel 1) Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122960895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288.6. 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
	CLIC1	NM_001288.6	MANE Select	c.611G>C	p.Arg204Pro	missense	Exon 6 of 6	NP_001279.2
	CLIC1	NM_001287593.1		c.611G>C	p.Arg204Pro	missense	Exon 7 of 7	NP_001274522.1	O00299
	CLIC1	NM_001287594.3		c.611G>C	p.Arg204Pro	missense	Exon 7 of 7	NP_001274523.1	O00299

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC1	ENST00000375784.8	TSL:1 MANE Select	c.611G>C	p.Arg204Pro	missense	Exon 6 of 6	ENSP00000364940.3	O00299
	CLIC1	ENST00000375780.6	TSL:1	c.611G>C	p.Arg204Pro	missense	Exon 7 of 7	ENSP00000364935.2	O00299
	CLIC1	ENST00000864998.1		c.620G>C	p.Arg207Pro	missense	Exon 6 of 6	ENSP00000535057.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460650 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726638

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.49
Sift	Benign	0.15	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.43
MutPred		0.54		Loss of methylation at R204 (P = 0.0158)
MVP		0.83
MPC		0.67
ClinPred		0.40	T
GERP RS		3.0
PromoterAI		-0.052	Neutral
Varity_R		0.72
gMVP		0.56
Mutation Taster		=68/32	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: rs373588470; hg19: chr6-31698734;