4-75556287-A-G

Position:

• chr4-75556287-A-G

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+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 932,436 control chromosomes in the GnomAD database, including 2,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (253 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1832 hom.)
• Consequence: ODAPH NM_178497.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.440

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=-0.83).
• BP6: Variant 4-75556287-A-G is Benign according to our data. Variant chr4-75556287-A-G is described in ClinVar as [Benign]. Clinvar id is 1250554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75556287-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAPH	NM_178497.5	c.67+138A>G		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+138A>G		intron_variant		1	NM_178497.5	ENSP00000311307.5

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7426 AN: 152200 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0415

GnomAD4 exome AF: 0.0627 AC: 48890 AN: 780118 Hom.: 1832 AF XY: 0.0624 AC XY: 25086 AN XY: 402028

Gnomad4 AFR exome AF: 0.00979

Gnomad4 AMR exome AF: 0.0269

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.000207

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0742

Gnomad4 NFE exome AF: 0.0733

Gnomad4 OTH exome AF: 0.0584

GnomAD4 genome AF: 0.0488 AC: 7430 AN: 152318 Hom.: 253 Cov.: 32 AF XY: 0.0499 AC XY: 3717 AN XY: 74472

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0648 Hom.: 160

Bravo AF: 0.0433

Asia WGS AF: 0.0180 AC: 65 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	-0.83
CADD	Benign	5.2
DANN	Benign	0.59

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: rs17214357; hg19: chr4-76481497;