rs17468190

chr6-46839202-G-T

Variant summary

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

The NM_005588.3(MEP1A):c.*66G>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 0.393 in 1,320,432 control chromosomes in the GnomAD database, including 97,369 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 0.38 (9465 hom., cov: 32)
  • Exomes 𝑓: 0.39 (87904 hom.)
• Consequence: MEP1A NM_005588.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

MEP1A (HGNC:7015): (meprin A subunit alpha) Predicted to enable metalloendopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. Part of meprin A complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEP1A	NM_005588.3	c.*66G>T		3_prime_UTR_variant	14/14	ENST00000230588.9
MEP1A	XM_011514628.2	c.*66G>T		3_prime_UTR_variant	13/13
MEP1A	XM_011514629.3	c.2084+3653G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEP1A	ENST00000230588.9	c.*66G>T		3_prime_UTR_variant	14/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2			downstream_gene_variant		1
MEP1A	ENST00000680229.1			downstream_gene_variant
MEP1A	ENST00000680769.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.383 AC: 52283 AN: 136648 Hom.: 9456 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.469

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.394 AC: 466375 AN: 1183692 Hom.: 87904 Cov.: 17 AF XY: 0.396 AC XY: 232422 AN XY: 586278

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.383 AC: 52323 AN: 136740 Hom.: 9465 Cov.: 32 AF XY: 0.384 AC XY: 25578 AN XY: 66616

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.394

Alfa AF: 0.363 Hom.: 1938

Bravo AF: 0.340

Asia WGS AF: 0.341 AC: 1188 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.068
Dann	Benign	0.35

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: rs17468190; hg19: chr6-46806939; COSMIC: COSV57921889;