rs17000647

Variant names:

• chr4-75556520-C-A
• rs17000647
• NM_178497.5:c.67+371C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-75556520-C-A
• chr4-75556520-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta hypomaturation type 2A4

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178497.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAPH	NM_178497.5	MANE Select	c.67+371C>A		intron	N/A	NP_848592.2	Q17RF5-1
	ODAPH	NM_001206981.2		c.68-21C>A		intron	N/A	NP_001193910.1	Q17RF5-2
	ODAPH	NM_001257072.2		c.67+371C>A		intron	N/A	NP_001244001.1	A0A087WV33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAPH	ENST00000311623.9	TSL:1 MANE Select	c.67+371C>A		intron	N/A	ENSP00000311307.5	Q17RF5-1
	ODAPH	ENST00000511093.5	TSL:1	n.67+371C>A		intron	N/A	ENSP00000421429.1	D6RFW7
	ODAPH	ENST00000435974.2	TSL:2	c.68-21C>A		intron	N/A	ENSP00000406925.2	Q17RF5-2

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

GnomAD2 exomes AF: 0.0152 AC: 1955 AN: 128544 AF XY: 0.0148

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 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

African (AFR) AF: 0.00425 AC: 134 AN: 31516

American (AMR) AF: 0.00995 AC: 355 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 690 AN: 25156

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35710

South Asian (SAS) AF: 0.00329 AC: 260 AN: 79112

European-Finnish (FIN) AF: 0.0123 AC: 413 AN: 33462

Middle Eastern (MID) AF: 0.0142 AC: 81 AN: 5694

European-Non Finnish (NFE) AF: 0.0259 AC: 27822 AN: 1073920

Other (OTH) AF: 0.0185 AC: 1068 AN: 57738

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

African (AFR) AF: 0.00577 AC: 240 AN: 41572

American (AMR) AF: 0.0136 AC: 208 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4826

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0259 AC: 1759 AN: 68036

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0203 Hom.: 70

Bravo AF: 0.0154

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.40
PhyloP100		0.11
PromoterAI		-0.0068	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17000647; hg19: chr4-76481730;