rs1046512

Positions:

• chr3-36990805-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014805.4(EPM2AIP1):​c.*449T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 984,204 control chromosomes in the GnomAD database, including 92,988 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 0.32 (9819 hom., cov: 32)
  • Exomes 𝑓: 0.44 (83169 hom.)
• Consequence: EPM2AIP1 NM_014805.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

Genes affected

EPM2AIP1 (HGNC:19735): (EPM2A interacting protein 1) The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless. [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 (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2AIP1	NM_014805.4	c.*449T>G		3_prime_UTR_variant	1/1	ENST00000322716.8	NP_055620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2AIP1	ENST00000322716	c.*449T>G		3_prime_UTR_variant	1/1		NM_014805.4	ENSP00000406027.1
EPM2AIP1	ENST00000624586.1	c.388-370T>G		intron_variant		5		ENSP00000485091.1
EPM2AIP1	ENST00000623924.1	c.63-370T>G		intron_variant		5		ENSP00000485489.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49095 AN: 151970 Hom.: 9817 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.442 AC: 367638 AN: 832116 Hom.: 83169 Cov.: 29 AF XY: 0.442 AC XY: 169913 AN XY: 384296

Gnomad4 AFR exome AF: 0.0952

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.323 AC: 49101 AN: 152088 Hom.: 9819 Cov.: 32 AF XY: 0.318 AC XY: 23623 AN XY: 74332

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.326

Alfa AF: 0.428 Hom.: 13843

Bravo AF: 0.314

Asia WGS AF: 0.173 AC: 609 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	8.0
DANN	Benign	0.66

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: rs1046512; hg19: chr3-37032296;