4-75556365-A-C

Position:

• chr4-75556365-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178497.5(ODAPH):​c.67+216A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,116 control chromosomes in the GnomAD database, including 3,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3473 hom., cov: 32)
• Consequence: ODAPH NM_178497.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-75556365-A-C is Benign according to our data. Variant chr4-75556365-A-C is described in ClinVar as [Benign]. Clinvar id is 1268128.Status of the report is criteria_provided_single_submitter, 1 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+216A>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+216A>C		intron_variant		1	NM_178497.5	ENSP00000311307.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31782 AN: 151998 Hom.: 3466 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31794 AN: 152116 Hom.: 3473 Cov.: 32 AF XY: 0.214 AC XY: 15881 AN XY: 74360

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.220

Alfa AF: 0.153 Hom.: 418

Bravo AF: 0.204

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
CADD	Benign	1.8
DANN	Benign	0.34

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: rs17214392; hg19: chr4-76481575;