4-87611100-T-C

Position:

• chr4-87611100-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014208.3(DSPP):​c.51+141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 863,322 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (24 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (18 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Likely 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 4-87611100-T-C is Benign according to our data. Variant chr4-87611100-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1197925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00908 (1379/151872) while in subpopulation AFR AF= 0.0275 (1137/41414). AF 95% confidence interval is 0.0261. There are 24 homozygotes in gnomad4. There are 648 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1379 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSPP	NM_014208.3	c.51+141T>C		intron_variant		ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.51+141T>C		intron_variant			NM_014208.3	P1
	ENST00000506480.5	n.323-42567A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00907 AC: 1376 AN: 151754 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00513

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00261 AC: 1854 AN: 711450 Hom.: 18 AF XY: 0.00270 AC XY: 1010 AN XY: 374672

Gnomad4 AFR exome AF: 0.0282

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.00348

Gnomad4 EAS exome AF: 0.0000299

Gnomad4 SAS exome AF: 0.00503

Gnomad4 FIN exome AF: 0.000532

Gnomad4 NFE exome AF: 0.00133

Gnomad4 OTH exome AF: 0.00488

GnomAD4 genome AF: 0.00908 AC: 1379 AN: 151872 Hom.: 24 Cov.: 31 AF XY: 0.00873 AC XY: 648 AN XY: 74252

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.00512

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0109

Asia WGS AF: 0.00318 AC: 12 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.43

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: rs72868621; hg19: chr4-88532252;