4-75556418-A-C

Position:

• chr4-75556418-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178497.5(ODAPH):​c.67+269A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 788,244 control chromosomes in the GnomAD database, including 18,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3478 hom., cov: 32)
  • Exomes 𝑓: 0.21 (14688 hom.)
• Consequence: ODAPH NM_178497.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.176

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-75556418-A-C is Benign according to our data. Variant chr4-75556418-A-C is described in ClinVar as [Benign]. Clinvar id is 1239054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAPH	NM_178497.5	c.67+269A>C		intron_variant		ENST00000311623.9	NP_848592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAPH	ENST00000311623.9	c.67+269A>C		intron_variant		1	NM_178497.5	ENSP00000311307.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31822 AN: 151976 Hom.: 3471 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.210 AC: 133831 AN: 636150 Hom.: 14688 AF XY: 0.210 AC XY: 70227 AN XY: 334236

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.209 AC: 31834 AN: 152094 Hom.: 3478 Cov.: 32 AF XY: 0.214 AC XY: 15884 AN XY: 74342

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.220

Alfa AF: 0.214 Hom.: 453

Bravo AF: 0.205

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.57
DANN	Benign	0.51

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: rs62318656; hg19: chr4-76481628; COSMIC: COSV61141463;