rs2247952

chr4-17519153-G-Achr4-17519153-G-Cchr4-17519153-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CLRN2	NM_001079827.2	c.253+3634G>A		intron_variant		ENST00000511148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLRN2	ENST00000511148.2	c.253+3634G>A		intron_variant		1	NM_001079827.2	P1

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.358

Alfa AF: 0.340 Hom.: 1987

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2247952; hg19: chr4-17520776;