ENST00000452617.8:n.575-2677T>G

Variant names:

• chr6-145825684-T-G
• rs12190966
• ENST00000452617.8:n.575-2677T>G

Variant summary

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

The ENST00000452617.8(EPM2A-DT):​n.575-2677T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,952 control chromosomes in the GnomAD database, including 16,210 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 0.45 (16210 hom., cov: 32)
• Consequence: EPM2A-DT ENST00000452617.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 3 publications found

Genes affected

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPM2A-DT	NR_038244.1	n.557-2677T>G		intron_variant	Intron 1 of 3
EPM2A-DT	NR_038245.1	n.557-2677T>G		intron_variant	Intron 1 of 2
EPM2A-DT	NR_038246.1	n.53-2677T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2A-DT	ENST00000452617.8	n.575-2677T>G		intron_variant	Intron 1 of 3	1
EPM2A-DT	ENST00000606388.6	n.597-2677T>G		intron_variant	Intron 1 of 3	1
EPM2A-DT	ENST00000627375.2	n.560-2677T>G		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68830 AN: 151832 Hom.: 16185 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.453 AC: 68902 AN: 151952 Hom.: 16210 Cov.: 32 AF XY: 0.456 AC XY: 33834 AN XY: 74264

African (AFR) AF: 0.561 AC: 23220 AN: 41422

American (AMR) AF: 0.328 AC: 5003 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1701 AN: 5150

South Asian (SAS) AF: 0.488 AC: 2346 AN: 4808

European-Finnish (FIN) AF: 0.508 AC: 5367 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28424 AN: 67938

Other (OTH) AF: 0.441 AC: 934 AN: 2116

Alfa AF: 0.432 Hom.: 1892

Bravo AF: 0.445

Asia WGS AF: 0.457 AC: 1589 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12190966; hg19: chr6-146146820;