rs9311149

Positions:

• chr3-36988684-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014805.4(EPM2AIP1):​c.*2570G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,850 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21380 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: EPM2AIP1 NM_014805.4 3_prime_UTR
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: 0.120

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-36988684-C-A is Benign according to our data. Variant chr3-36988684-C-A is described in ClinVar as [Benign]. Clinvar id is 89594.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr3-36988684-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPM2AIP1	NM_014805.4	c.*2570G>T		3_prime_UTR_variant	1/1	ENST00000322716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPM2AIP1	ENST00000322716.8	c.*2570G>T		3_prime_UTR_variant	1/1		NM_014805.4	P1
EPM2AIP1	ENST00000623924.1	c.124-1455G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78366 AN: 151726 Hom.: 21350 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.517 AC: 78453 AN: 151844 Hom.: 21380 Cov.: 31 AF XY: 0.507 AC XY: 37616 AN XY: 74186

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.497

Alfa AF: 0.521 Hom.: 21591

Bravo AF: 0.524

Asia WGS AF: 0.237 AC: 828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.59

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: rs9311149; hg19: chr3-37030175;