dbSNP rs17000647: ODAPH:c.67+371C>A (chr4-75556520-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Variant links:

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]

ODAPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAPH	NM_178497.5 link	c.67+371C>A		intron_variant	Intron 1 of 1	ENST00000311623.9	NP_848592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAPH	ENST00000311623.9 link	c.67+371C>A		intron_variant	Intron 1 of 1	1	NM_178497.5	ENSP00000311307.5		Q17RF5-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2501

AN:

152200

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0148

AC XY:

1040

AN XY:

70386

show subpopulations

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.:

AF XY:

0.0220

AC XY:

14968

AN XY:

680296

show subpopulations

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.:

Cov.:

AF XY:

0.0155

AC XY:

1153

AN XY:

74480

show subpopulations

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.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.00231

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over