4-87834676-T-C

Variant names:

• chr4-87834676-T-C
• rs7698623
• NM_020203.6:c.-12-27T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020203.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPE	NM_020203.6	MANE Select	c.-12-27T>C		intron	N/A	NP_064588.1	Q9NQ76-1
	MEPE	NM_001291183.2		c.-12-27T>C		intron	N/A	NP_001278112.1	Q9NQ76-2
	MEPE	NM_001184694.3		c.-12-27T>C		intron	N/A	NP_001171623.1	Q9NQ76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPE	ENST00000361056.4	TSL:1 MANE Select	c.-12-27T>C		intron	N/A	ENSP00000354341.3	Q9NQ76-1
	MEPE	ENST00000560249.6	TSL:1	c.-12-27T>C		intron	N/A	ENSP00000453994.2	A0A8J9B5S1
	MEPE	ENST00000395102.8	TSL:5	c.-12-27T>C		intron	N/A	ENSP00000378534.4	Q9NQ76-2

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

GnomAD2 exomes AF: 0.941 AC: 231072 AN: 245526 AF XY: 0.940

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 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

African (AFR) AF: 0.976 AC: 31739 AN: 32506

American (AMR) AF: 0.984 AC: 42453 AN: 43164

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 24973 AN: 25710

East Asian (EAS) AF: 0.828 AC: 32745 AN: 39538

South Asian (SAS) AF: 0.946 AC: 79791 AN: 84332

European-Finnish (FIN) AF: 0.939 AC: 49797 AN: 53004

Middle Eastern (MID) AF: 0.981 AC: 5585 AN: 5694

European-Non Finnish (NFE) AF: 0.935 AC: 1016754 AN: 1087330

Other (OTH) AF: 0.935 AC: 55443 AN: 59268

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

African (AFR) AF: 0.977 AC: 40583 AN: 41558

American (AMR) AF: 0.977 AC: 14943 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3364 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4182 AN: 5174

South Asian (SAS) AF: 0.949 AC: 4584 AN: 4828

European-Finnish (FIN) AF: 0.940 AC: 9973 AN: 10612

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63731 AN: 68022

Other (OTH) AF: 0.955 AC: 2020 AN: 2116

Alfa AF: 0.944 Hom.: 217088

Bravo AF: 0.953

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.40
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7698623; hg19: chr4-88755828; COSMIC: COSV63072889;