chr4-87609311-C-T

Position:

• chr4-87609311-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014208.3(DSPP):​c.-29+691C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,124 control chromosomes in the GnomAD database, including 6,054 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6054 hom., cov: 32)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSPP	NM_014208.3	c.-29+691C>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.-29+691C>T		intron_variant			NM_014208.3	ENSP00000498766	P1
	ENST00000506480.5	n.323-40778G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39921 AN: 152006 Hom.: 6044 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.263 AC: 39945 AN: 152124 Hom.: 6054 Cov.: 32 AF XY: 0.262 AC XY: 19455 AN XY: 74362

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.281

Alfa AF: 0.312 Hom.: 13736

Bravo AF: 0.254

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.079
DANN	Benign	0.44

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: rs2615487; hg19: chr4-88530463;