rs4714952

Positions:

• chr6-46834633-G-A
• chr6-46834633-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005588.3(MEP1A):​c.1665G>A​(p.Thr555=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,609,818 control chromosomes in the GnomAD database, including 342,869 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 0.70 (38606 hom., cov: 30)
  • Exomes 𝑓: 0.64 (304263 hom.)
• Consequence: MEP1A NM_005588.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-3.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEP1A	NM_005588.3	c.1665G>A	p.Thr555=	synonymous_variant	12/14	ENST00000230588.9
MEP1A	XM_011514628.2	c.1749G>A	p.Thr583=	synonymous_variant	11/13
MEP1A	XM_011514629.3	c.1665G>A	p.Thr555=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEP1A	ENST00000230588.9	c.1665G>A	p.Thr555=	synonymous_variant	12/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2	c.1749G>A	p.Thr583=	synonymous_variant	11/13	1
MEP1A	ENST00000680769.1	n.1846G>A		non_coding_transcript_exon_variant	10/12
MEP1A	ENST00000680229.1	c.*850G>A		3_prime_UTR_variant, NMD_transcript_variant	12/14

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106778 AN: 151778 Hom.: 38545 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.684

GnomAD3 exomes AF: 0.668 AC: 167572 AN: 251016 Hom.: 57240 AF XY: 0.663 AC XY: 89887 AN XY: 135672

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.769

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.474

Gnomad SAS exome AF: 0.725

Gnomad FIN exome AF: 0.588

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.643 AC: 937889 AN: 1457920 Hom.: 304263 Cov.: 33 AF XY: 0.645 AC XY: 467577 AN XY: 725344

Gnomad4 AFR exome AF: 0.867

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.705

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.704 AC: 106902 AN: 151898 Hom.: 38606 Cov.: 30 AF XY: 0.700 AC XY: 51958 AN XY: 74222

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.685

Alfa AF: 0.672 Hom.: 14988

Bravo AF: 0.718

Asia WGS AF: 0.654 AC: 2275 AN: 3478

EpiCase AF: 0.638

EpiControl AF: 0.636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4714952; hg19: chr6-46802370;