4-87829584-A-T

Variant names:

• chr4-87829584-A-T
• rs727420
• NM_001184694.3:c.-12-5119A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000307815 (HGNC:58843):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MEPE	NM_001184694.3	c.-12-5119A>T		intron_variant	Intron 1 of 3		NP_001171623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEPE	ENST00000424957.8	c.-12-5119A>T		intron_variant	Intron 1 of 3	2		ENSP00000416984.3
ENSG00000307815	ENST00000829020.1	n.286-43136T>A		intron_variant	Intron 3 of 5
ENSG00000307815	ENST00000829021.1	n.341-43136T>A		intron_variant	Intron 3 of 4

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

African (AFR) AF: 0.240 AC: 9980 AN: 41508

American (AMR) AF: 0.214 AC: 3276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3462

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5192

South Asian (SAS) AF: 0.196 AC: 945 AN: 4818

European-Finnish (FIN) AF: 0.147 AC: 1558 AN: 10584

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18609 AN: 67976

Other (OTH) AF: 0.244 AC: 516 AN: 2114

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs727420; hg19: chr4-88750736;