4-87829584-A-T

Position:

• chr4-87829584-A-T

Variant summary

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

The NM_001184694.3(MEPE):​c.-12-5119A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,136 control chromosomes in the GnomAD database, including 4,595 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 0.24 (4595 hom., cov: 33)
• Consequence: MEPE NM_001184694.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEPE	NM_001184694.3	c.-12-5119A>T		intron_variant			NP_001171623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEPE	ENST00000424957.8	c.-12-5119A>T		intron_variant		2		ENSP00000416984	P2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36060 AN: 152018 Hom.: 4590 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.237 AC: 36087 AN: 152136 Hom.: 4595 Cov.: 33 AF XY: 0.228 AC XY: 16964 AN XY: 74392

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.244

Alfa AF: 0.114 Hom.: 182

Bravo AF: 0.243

Asia WGS AF: 0.108 AC: 379 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.36

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: rs727420; hg19: chr4-88750736;