4-87610648-C-T

Position:

• chr4-87610648-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014208.3(DSPP):​c.-28-233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,986 control chromosomes in the GnomAD database, including 6,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.27 (6145 hom., cov: 32)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.402

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]

ENSG00000249001 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-87610648-C-T is Benign according to our data. Variant chr4-87610648-C-T is described in ClinVar as [Benign]. Clinvar id is 1179349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSPP	NM_014208.3	c.-28-233C>T		intron_variant		ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.-28-233C>T		intron_variant			NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42115G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40547 AN: 151868 Hom.: 6135 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40575 AN: 151986 Hom.: 6145 Cov.: 32 AF XY: 0.266 AC XY: 19749 AN XY: 74304

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.284

Alfa AF: 0.270 Hom.: 1091

Bravo AF: 0.259

Asia WGS AF: 0.445 AC: 1545 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2627699; hg19: chr4-88531800; COSMIC: COSV56817082; COSMIC: COSV56817082;