Variant 4-87656421-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004407.4(DMP1):c.-21-51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,046,094 control chromosomes in the GnomAD database, including 291,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46936 hom., cov: 32)

Exomes 𝑓: 0.74 ( 244445 hom. )

Consequence

DMP1
NM_004407.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.545

Variant links:

Genes affected

DMP1 (HGNC:2932): (dentin matrix acidic phosphoprotein 1) Dentin matrix acidic phosphoprotein is an extracellular matrix protein and a member of the small integrin binding ligand N-linked glycoprotein family. This protein, which is critical for proper mineralization of bone and dentin, is present in diverse cells of bone and tooth tissues. The protein contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. In undifferentiated osteoblasts it is primarily a nuclear protein that regulates the expression of osteoblast-specific genes. During osteoblast maturation the protein becomes phosphorylated and is exported to the extracellular matrix, where it orchestrates mineralized matrix formation. Mutations in the gene are known to cause autosomal recessive hypophosphatemia, a disease that manifests as rickets and osteomalacia. The gene structure is conserved in mammals. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DMP1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-87656421-A-G is Benign according to our data. Variant chr4-87656421-A-G is described in ClinVar as [Benign]. Clinvar id is 1179610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DMP1	NM_004407.4 linkuse as main transcript	c.-21-51A>G	intron_variant	ENST00000339673.11
DMP1	NM_001079911.3 linkuse as main transcript	c.-21-51A>G	intron_variant
DMP1	XM_011531705.3 linkuse as main transcript	c.67-51A>G	intron_variant
DMP1	XM_011531706.3 linkuse as main transcript	c.67-51A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMP1	ENST00000339673.11 linkuse as main transcript	c.-21-51A>G		intron_variant		1	NM_004407.4	P1	Q13316-1
	ENST00000506480.5 linkuse as main transcript	n.322+16569T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118688

AN:

152052

Hom.:

46880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.804

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.766

GnomAD4 exome

AF:

0.736

AC:

658224

AN:

893924

Hom.:

244445

AF XY:

0.733

AC XY:

343432

AN XY:

468558

show subpopulations

Gnomad4 AFR exome

AF:

0.890

Gnomad4 AMR exome

AF:

0.858

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.861

Gnomad4 SAS exome

AF:

0.719

Gnomad4 FIN exome

AF:

0.775

Gnomad4 NFE exome

AF:

0.719

Gnomad4 OTH exome

AF:

0.744

GnomAD4 genome

AF:

0.781

AC:

118802

AN:

152170

Hom.:

46936

Cov.:

AF XY:

0.782

AC XY:

58197

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.888

Gnomad4 AMR

AF:

0.804

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.778

Gnomad4 NFE

AF:

0.719

Gnomad4 OTH

AF:

0.768

Alfa

AF:

0.750

Hom.:

5437

Bravo

AF:

0.790

Asia WGS

AF:

0.831

AC:

2892

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.79

DANN

Benign

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over