4-87650292-CA-C

Position:

• chr4-87650292-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004407.4(DMP1):​c.-112del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,148 control chromosomes in the GnomAD database, including 2,221 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2221 hom., cov: 29)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DMP1 NM_004407.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23

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 -10 ACMG points.

• BP6: Variant 4-87650292-CA-C is Benign according to our data. Variant chr4-87650292-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 369444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMP1	NM_004407.4	c.-112del		5_prime_UTR_variant	1/6	ENST00000339673.11
DMP1	NM_001079911.3	c.-112del		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMP1	ENST00000339673.11	c.-112del		5_prime_UTR_variant	1/6	1	NM_004407.4	P1
	ENST00000506480.5	n.322+22697del		intron_variant, non_coding_transcript_variant		3
DMP1	ENST00000282479.8			upstream_gene_variant		1
DMP1	ENST00000682752.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22963 AN: 152026 Hom.: 2221 Cov.: 29

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.151 AC: 22963 AN: 152144 Hom.: 2221 Cov.: 29 AF XY: 0.149 AC XY: 11083 AN XY: 74402

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.188

Alfa AF: 0.177 Hom.: 329

Bravo AF: 0.153

Asia WGS AF: 0.104 AC: 365 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypophosphatemic Rickets, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36089093; hg19: chr4-88571444;