chr4-87611030-A-AGTGTGTGTGT

Position:

• chr4-87611030-A-AGTGTGTGTGT

Variant summary

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

The NM_014208.3(DSPP):​c.51+95_51+104dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 819,016 control chromosomes in the GnomAD database, including 252 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (208 hom., cov: 0)
  • Exomes 𝑓: 0.024 (44 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257

Genes affected

DSPP (HGNC:3054): (dentin sialophosphoprotein) This gene encodes a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins. The encoded preproprotein is secreted by odontoblasts and proteolytically processed to generate two principal proteins of the dentin extracellular matrix of the tooth, dentin sialoprotein and dentin phosphoprotein. These two protein products may play distinct but related roles in dentin mineralization. Mutations in this gene are associated with dentinogenesis imperfecta and dentin dysplasia. This gene is present in a gene cluster on chromosome 4. Allelic differences due to repeat polymorphisms have been found for this gene. [provided by RefSeq, Jan 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-87611030-A-AGTGTGTGTGT is Benign according to our data. Variant chr4-87611030-A-AGTGTGTGTGT is described in ClinVar as [Benign]. Clinvar id is 1289383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSPP	NM_014208.3	c.51+95_51+104dup		intron_variant		ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.51+95_51+104dup		intron_variant			NM_014208.3	P1
	ENST00000506480.5	n.323-42498_323-42497insACACACACAC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 6731 AN: 145510 Hom.: 207 Cov.: 0

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.0134

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0552

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0400

GnomAD4 exome AF: 0.0241 AC: 16204 AN: 673406 Hom.: 44 AF XY: 0.0235 AC XY: 8492 AN XY: 360954

Gnomad4 AFR exome AF: 0.0708

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0297

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.0561

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0463 AC: 6737 AN: 145610 Hom.: 208 Cov.: 0 AF XY: 0.0459 AC XY: 3237 AN XY: 70586

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0344

Gnomad4 EAS AF: 0.0134

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0401

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 21, 2019

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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: rs33940466; hg19: chr4-88532182;