rs1046512

Variant names:

• chr3-36990805-A-C
• rs1046512
• NM_014805.4:c.*449T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPM2AIP1	NM_014805.4	c.*449T>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000322716.8	NP_055620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2AIP1	ENST00000322716.8	c.*449T>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_014805.4	ENSP00000406027.1
EPM2AIP1	ENST00000624586.1	c.388-370T>G		intron_variant	Intron 1 of 1	5		ENSP00000485091.1
EPM2AIP1	ENST00000623924.1	c.63-370T>G		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.0952 AC: 1502 AN: 15784

American (AMR) AF: 0.382 AC: 392 AN: 1026

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 2067 AN: 5160

East Asian (EAS) AF: 0.0671 AC: 244 AN: 3636

South Asian (SAS) AF: 0.246 AC: 4060 AN: 16476

European-Finnish (FIN) AF: 0.395 AC: 113 AN: 286

Middle Eastern (MID) AF: 0.341 AC: 552 AN: 1620

European-Non Finnish (NFE) AF: 0.458 AC: 348092 AN: 760848

Other (OTH) AF: 0.389 AC: 10616 AN: 27280

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

African (AFR) AF: 0.111 AC: 4607 AN: 41518

American (AMR) AF: 0.378 AC: 5773 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3468

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5190

South Asian (SAS) AF: 0.228 AC: 1101 AN: 4826

European-Finnish (FIN) AF: 0.365 AC: 3844 AN: 10536

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30758 AN: 67962

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.425 Hom.: 16316

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
PhyloP100		0.56
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: rs1046512; hg19: chr3-37032296;