chr4-87609311-C-T

Variant names:

• chr4-87609311-C-T
• rs2615487
• NM_014208.3:c.-29+691C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

DSPP Gene-Disease associations (from GenCC):

• deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

  Inheritance: AD, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• dentinogenesis imperfecta

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dentinogenesis imperfecta type 2

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• dentinogenesis imperfecta type 3

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• dentin dysplasia type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dentin dysplasia type II

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000249001 (HGNC:58144):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	NM_014208.3	MANE Select	c.-29+691C>T		intron	N/A	NP_055023.2
	DMP1-AS1	NR_198971.1		n.367-40778G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	ENST00000651931.1	MANE Select	c.-29+691C>T		intron	N/A	ENSP00000498766.1
	ENSG00000249001	ENST00000506480.5	TSL:3	n.323-40778G>A		intron	N/A
	ENSG00000249001	ENST00000829286.1		n.357-40778G>A		intron	N/A

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

African (AFR) AF: 0.121 AC: 5012 AN: 41512

American (AMR) AF: 0.242 AC: 3700 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2937 AN: 5168

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4828

European-Finnish (FIN) AF: 0.293 AC: 3094 AN: 10572

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21765 AN: 67972

Other (OTH) AF: 0.281 AC: 590 AN: 2102

Alfa AF: 0.309 Hom.: 17267

Bravo AF: 0.254

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.079
DANN	Benign	0.44
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2615487; hg19: chr4-88530463;