chr4-17519153-G-A

Variant names:

• chr4-17519153-G-A
• rs2247952
• NM_001079827.2:c.253+3634G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079827.2(CLRN2):​c.253+3634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,008 control chromosomes in the GnomAD database, including 8,733 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 0.33 (8733 hom., cov: 33)
• Consequence: CLRN2 NM_001079827.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• 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):

• hearing loss, autosomal recessive 117

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLRN2	NM_001079827.2	c.253+3634G>A		intron_variant	Intron 1 of 2	ENST00000511148.2	NP_001073296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLRN2	ENST00000511148.2	c.253+3634G>A		intron_variant	Intron 1 of 2	1	NM_001079827.2	ENSP00000424711.2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50428 AN: 151890 Hom.: 8735 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.332 AC: 50446 AN: 152008 Hom.: 8733 Cov.: 33 AF XY: 0.334 AC XY: 24788 AN XY: 74314

African (AFR) AF: 0.265 AC: 10977 AN: 41446

American (AMR) AF: 0.465 AC: 7101 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2409 AN: 5168

South Asian (SAS) AF: 0.358 AC: 1720 AN: 4810

European-Finnish (FIN) AF: 0.301 AC: 3180 AN: 10566

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22709 AN: 67964

Other (OTH) AF: 0.358 AC: 757 AN: 2114

Alfa AF: 0.343 Hom.: 3584

Bravo AF: 0.343

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.47
Mutation Taster		=100/0	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: rs2247952; hg19: chr4-17520776;