rs200173085

Variant names:

• chr4-17526856-C-T
• rs200173085
• NM_001079827.2:c.473C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-17526856-C-T
• chr4-17526856-C-A
• chr4-17526856-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001079827.2(CLRN2):​c.473C>T​(p.Ala158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CLRN2 NM_001079827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 4 publications found

Genes affected

CLRN2 (HGNC:33939): (clarin 2) This gene belongs to the clarin family of genes. The clarins appear to belong to a large superfamily of small integral membrane glycoproteins with four transmembrane domains. The exact function of this gene is unknown. [provided by RefSeq, Oct 2008]

CLRN2 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive 117

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26543126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079827.2. 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
	CLRN2	NM_001079827.2	MANE Select	c.473C>T	p.Ala158Val	missense	Exon 3 of 3	NP_001073296.1	A0PK11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN2	ENST00000511148.2	TSL:1 MANE Select	c.473C>T	p.Ala158Val	missense	Exon 3 of 3	ENSP00000424711.2	A0PK11

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000963 AC: 24 AN: 249190 AF XY: 0.0000888

Gnomad AFR exome AF: 0.000969

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 226 AN: 1461690 Hom.: 0 Cov.: 31 AF XY: 0.000151 AC XY: 110 AN XY: 727122

African (AFR) AF: 0.00179 AC: 60 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1111848

Other (OTH) AF: 0.000381 AC: 23 AN: 60374

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37 AN XY: 74456

African (AFR) AF: 0.00159 AC: 66 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.000552

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00147 AC: 6

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.0000992 AC: 12

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

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	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.36
Sift	Benign	0.067	T
Sift4G	Benign	0.099	T
Polyphen		0.91	P
Vest4		0.57
MVP		0.74
MPC		0.23
ClinPred		0.076	T
GERP RS		4.9
Varity_R		0.091
gMVP		0.64
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200173085; hg19: chr4-17528479; COSMIC: COSV71825238;