rs17000647

chr4-75556520-C-Achr4-75556520-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_178497.5(ODAPH):c.67+371C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,530,292 control chromosomes in the GnomAD database, including 446 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 0.016 (25 hom., cov: 32)
  • Exomes 𝑓: 0.022 (421 hom.)
• Consequence: ODAPH NM_178497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

Genes affected

ODAPH (HGNC:26300): (odontogenesis associated phosphoprotein) Dental enamel forms the outer cap of teeth and is the hardest substance found in vertebrates. This gene is thought to encode an extracellular matrix acidic phosphoprotein that has a function in enamel mineralization during amelogenesis. Mutations in this gene are associated with recessive hypomineralized amelogenesis imperfecta. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2501/152318) while in subpopulation NFE AF= 0.0259 (1759/68036). AF 95% confidence interval is 0.0248. There are 25 homozygotes in gnomad4. There are 1153 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAPH	NM_178497.5	c.67+371C>A		intron_variant		ENST00000311623.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAPH	ENST00000311623.9	c.67+371C>A		intron_variant		1	NM_178497.5	P1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2501 AN: 152200 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0152 AC: 1955 AN: 128544 Hom.: 28 AF XY: 0.0148 AC XY: 1040 AN XY: 70386

Gnomad AFR exome AF: 0.00540

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00358

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.0255

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0224 AC: 30826 AN: 1377974 Hom.: 421 Cov.: 29 AF XY: 0.0220 AC XY: 14968 AN XY: 680296

Gnomad4 AFR exome AF: 0.00425

Gnomad4 AMR exome AF: 0.00995

Gnomad4 ASJ exome AF: 0.0274

Gnomad4 EAS exome AF: 0.0000840

Gnomad4 SAS exome AF: 0.00329

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0259

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0164 AC: 2501 AN: 152318 Hom.: 25 Cov.: 32 AF XY: 0.0155 AC XY: 1153 AN XY: 74480

Gnomad4 AFR AF: 0.00577

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0215 Hom.: 42

Bravo AF: 0.0154

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.3
Dann	Benign	0.40

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: rs17000647; hg19: chr4-76481730;