4-87657158-A-G

Position:

• chr4-87657158-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004407.4(DMP1):​c.102+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 833,952 control chromosomes in the GnomAD database, including 236,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (46900 hom., cov: 32)
  • Exomes 𝑓: 0.74 (189423 hom.)
• Consequence: DMP1 NM_004407.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-87657158-A-G is Benign according to our data. Variant chr4-87657158-A-G is described in ClinVar as [Benign]. Clinvar id is 1227806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMP1	NM_004407.4	c.102+79A>G		intron_variant		ENST00000339673.11
LOC105377323	XR_938960.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMP1	ENST00000339673.11	c.102+79A>G		intron_variant		1	NM_004407.4	P1
	ENST00000506480.5	n.322+15832T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118633 AN: 152040 Hom.: 46845 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.742 AC: 505751 AN: 681794 Hom.: 189423 Cov.: 9 AF XY: 0.738 AC XY: 266815 AN XY: 361566

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.861

Gnomad4 SAS exome AF: 0.723

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.724

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.780 AC: 118746 AN: 152158 Hom.: 46900 Cov.: 32 AF XY: 0.782 AC XY: 58182 AN XY: 74388

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: 0.779

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.768

Alfa AF: 0.759 Hom.: 6708

Bravo AF: 0.789

Asia WGS AF: 0.830 AC: 2882 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.79

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: rs2615479; hg19: chr4-88578310;