chr4-17522947-C-G

Variant names:

• chr4-17522947-C-G
• rs13147559
• NM_001079827.2:c.337C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079827.2(CLRN2):​c.337C>G​(p.Leu113Val) variant causes a missense change. The variant allele was found at a frequency of 0.129 in 1,613,840 control chromosomes in the GnomAD database, including 14,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (966 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13335 hom.)
• Consequence: CLRN2 NM_001079827.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.97
• Publications: 17 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018548369).
• BP6: Variant 4-17522947-C-G is Benign according to our data. Variant chr4-17522947-C-G is described in ClinVar as Benign. ClinVar VariationId is 1286756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

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.337C>G	p.Leu113Val	missense	Exon 2 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.337C>G	p.Leu113Val	missense	Exon 2 of 3	ENSP00000424711.2	A0PK11

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15687 AN: 152140 Hom.: 962 Cov.: 33

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0899

GnomAD2 exomes AF: 0.130 AC: 32385 AN: 249170 AF XY: 0.131

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.0950

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.132 AC: 192340 AN: 1461582 Hom.: 13335 Cov.: 32 AF XY: 0.132 AC XY: 96225 AN XY: 727064

African (AFR) AF: 0.0183 AC: 611 AN: 33476

American (AMR) AF: 0.147 AC: 6569 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 5275 AN: 26132

East Asian (EAS) AF: 0.0845 AC: 3355 AN: 39700

South Asian (SAS) AF: 0.137 AC: 11834 AN: 86240

European-Finnish (FIN) AF: 0.137 AC: 7317 AN: 53398

Middle Eastern (MID) AF: 0.0672 AC: 387 AN: 5758

European-Non Finnish (NFE) AF: 0.134 AC: 149120 AN: 1111800

Other (OTH) AF: 0.130 AC: 7872 AN: 60364

GnomAD4 genome AF: 0.103 AC: 15699 AN: 152258 Hom.: 966 Cov.: 33 AF XY: 0.104 AC XY: 7707 AN XY: 74444

African (AFR) AF: 0.0266 AC: 1107 AN: 41578

American (AMR) AF: 0.119 AC: 1819 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3470

East Asian (EAS) AF: 0.0906 AC: 469 AN: 5174

South Asian (SAS) AF: 0.142 AC: 686 AN: 4830

European-Finnish (FIN) AF: 0.139 AC: 1469 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9102 AN: 68008

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.131 Hom.: 1068

Bravo AF: 0.0988

TwinsUK AF: 0.128 AC: 473

ALSPAC AF: 0.123 AC: 474

ESP6500AA AF: 0.0297 AC: 127

ESP6500EA AF: 0.134 AC: 1141

ExAC AF: 0.128 AC: 15497

Asia WGS AF: 0.117 AC: 406 AN: 3478

EpiCase AF: 0.127

EpiControl AF: 0.121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.34
Sift	Benign	0.089	T
Sift4G	Benign	0.31	T
Polyphen		0.90	P
Vest4		0.14
MPC		0.70
ClinPred		0.030	T
GERP RS		4.2
Varity_R		0.24
gMVP		0.78
Mutation Taster		=85/15	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: rs13147559; hg19: chr4-17524570; COSMIC: COSV72512491;