4-87834676-T-C

Variant summary

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

The NM_020203.6(MEPE):c.-12-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,582,826 control chromosomes in the GnomAD database, including 696,172 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 0.95 (68690 hom., cov: 32)
  • Exomes 𝑓: 0.94 (627482 hom.)
• Consequence: MEPE NM_020203.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

Genes affected

MEPE (HGNC:13361): (matrix extracellular phosphoglycoprotein) This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEPE	NM_020203.6	c.-12-27T>C		intron_variant		ENST00000361056.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEPE	ENST00000361056.4	c.-12-27T>C		intron_variant		1	NM_020203.6	P2

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144429 AN: 152162 Hom.: 68632 Cov.: 32

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.955

GnomAD3 exomes AF: 0.941 AC: 231072 AN: 245526 Hom.: 109022 AF XY: 0.940 AC XY: 124782 AN XY: 132704

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.984

Gnomad ASJ exome AF: 0.971

Gnomad EAS exome AF: 0.797

Gnomad SAS exome AF: 0.949

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.941

Gnomad OTH exome AF: 0.954

GnomAD4 exome AF: 0.936 AC: 1339280 AN: 1430546 Hom.: 627482 Cov.: 24 AF XY: 0.936 AC XY: 667982 AN XY: 713298

Gnomad4 AFR exome AF: 0.976

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.971

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.939

Gnomad4 NFE exome AF: 0.935

Gnomad4 OTH exome AF: 0.935

GnomAD4 genome AF: 0.949 AC: 144545 AN: 152280 Hom.: 68690 Cov.: 32 AF XY: 0.950 AC XY: 70692 AN XY: 74446

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.949

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.955

Alfa AF: 0.940 Hom.: 143075

Bravo AF: 0.953

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.8
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7698623; hg19: chr4-88755828; COSMIC: COSV63072889;