chr4-87829584-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69
Variant links:
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]

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ACMG classification

Classification made for transcript

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
MEPENM_001184694.3 linkuse as main transcriptc.-12-5119A>T intron_variant NP_001171623.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEPEENST00000424957.8 linkuse as main transcriptc.-12-5119A>T intron_variant 2 ENSP00000416984 P2Q9NQ76-1

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs727420; hg19: chr4-88750736; API