4-70196591-C-A

Variant names:

• chr4-70196591-C-A
• rs61747755
• NM_017855.4:c.48C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_017855.4(ODAM):​c.48C>A​(p.Ala16Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,581,112 control chromosomes in the GnomAD database, including 15,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1111 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14107 hom.)
• Consequence: ODAM NM_017855.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0730
• Publications: 12 publications found

Genes affected

ODAM (HGNC:26043): (odontogenic, ameloblast associated) Involved in several processes, including positive regulation of GTPase activity; positive regulation of epithelial cell proliferation involved in wound healing; and positive regulation of macromolecule metabolic process. Located in several cellular components, including extracellular space; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 4-70196591-C-A is Benign according to our data. Variant chr4-70196591-C-A is described in ClinVar as Benign. ClinVar VariationId is 1326056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017855.4. 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
	ODAM	NM_017855.4	MANE Select	c.48C>A	p.Ala16Ala	synonymous	Exon 2 of 12	NP_060325.3
	ODAM	NM_001385579.1		c.48C>A	p.Ala16Ala	synonymous	Exon 2 of 11	NP_001372508.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAM	ENST00000683306.1	MANE Select	c.48C>A	p.Ala16Ala	synonymous	Exon 2 of 12	ENSP00000507531.1	A1E959
	ODAM	ENST00000396094.6	TSL:5	c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 11	ENSP00000379401.2	A1E959
	ODAM	ENST00000955828.1		c.48C>A	p.Ala16Ala	synonymous	Exon 2 of 12	ENSP00000625887.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15406 AN: 151780 Hom.: 1108 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.123 AC: 29843 AN: 241788 AF XY: 0.133

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.0758

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.00790

Gnomad FIN exome AF: 0.0919

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.132 AC: 188032 AN: 1429214 Hom.: 14107 Cov.: 28 AF XY: 0.136 AC XY: 96523 AN XY: 711710

African (AFR) AF: 0.0219 AC: 728 AN: 33168

American (AMR) AF: 0.0799 AC: 3529 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5481 AN: 25592

East Asian (EAS) AF: 0.00389 AC: 153 AN: 39358

South Asian (SAS) AF: 0.223 AC: 18646 AN: 83594

European-Finnish (FIN) AF: 0.0932 AC: 4945 AN: 53064

Middle Eastern (MID) AF: 0.201 AC: 1131 AN: 5640

European-Non Finnish (NFE) AF: 0.134 AC: 145410 AN: 1085570

Other (OTH) AF: 0.136 AC: 8009 AN: 59070

GnomAD4 genome AF: 0.101 AC: 15416 AN: 151898 Hom.: 1111 Cov.: 32 AF XY: 0.100 AC XY: 7445 AN XY: 74232

African (AFR) AF: 0.0266 AC: 1103 AN: 41502

American (AMR) AF: 0.108 AC: 1646 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 768 AN: 3466

East Asian (EAS) AF: 0.0111 AC: 57 AN: 5138

South Asian (SAS) AF: 0.227 AC: 1092 AN: 4814

European-Finnish (FIN) AF: 0.0853 AC: 900 AN: 10550

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9416 AN: 67902

Other (OTH) AF: 0.142 AC: 298 AN: 2104

Alfa AF: 0.125 Hom.: 2343

Bravo AF: 0.0983

Asia WGS AF: 0.120 AC: 416 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.6
DANN	Benign	0.68
PhyloP100		0.073
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs61747755; hg19: chr4-71062308; COSMIC: COSV68573277; COSMIC: COSV68573277;