rs3756132

Variant names:

• chr4-70196539-C-T
• rs3756132
• NM_017855.4:c.-5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017855.4(ODAM):​c.-5C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,539,130 control chromosomes in the GnomAD database, including 60,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5151 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55476 hom.)
• Consequence: ODAM NM_017855.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.00
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-70196539-C-T is Benign according to our data. Variant chr4-70196539-C-T is described in ClinVar as Benign. ClinVar VariationId is 1326082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 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.-5C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_060325.3
	ODAM	NM_017855.4	MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 12	NP_060325.3
	ODAM	NM_001385579.1		c.-5C>T		5_prime_UTR_premature_start_codon_gain	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.-5C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000507531.1	A1E959
	ODAM	ENST00000683306.1	MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 12	ENSP00000507531.1	A1E959
	ODAM	ENST00000396094.6	TSL:5	c.-5C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000379401.2	A1E959

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37757 AN: 151536 Hom.: 5144 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.260 AC: 56245 AN: 216450 AF XY: 0.276

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.271 AC: 376103 AN: 1387476 Hom.: 55476 Cov.: 27 AF XY: 0.279 AC XY: 192463 AN XY: 690370

African (AFR) AF: 0.163 AC: 5256 AN: 32312

American (AMR) AF: 0.144 AC: 6111 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 10079 AN: 24902

East Asian (EAS) AF: 0.309 AC: 11877 AN: 38494

South Asian (SAS) AF: 0.466 AC: 37043 AN: 79416

European-Finnish (FIN) AF: 0.233 AC: 12141 AN: 52012

Middle Eastern (MID) AF: 0.407 AC: 2154 AN: 5290

European-Non Finnish (NFE) AF: 0.261 AC: 275012 AN: 1055086

Other (OTH) AF: 0.286 AC: 16430 AN: 57392

GnomAD4 genome AF: 0.249 AC: 37787 AN: 151654 Hom.: 5151 Cov.: 32 AF XY: 0.251 AC XY: 18581 AN XY: 74090

African (AFR) AF: 0.174 AC: 7202 AN: 41390

American (AMR) AF: 0.217 AC: 3295 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1457 AN: 5110

South Asian (SAS) AF: 0.472 AC: 2275 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2351 AN: 10526

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18826 AN: 67824

Other (OTH) AF: 0.293 AC: 615 AN: 2100

Alfa AF: 0.277 Hom.: 3174

Bravo AF: 0.239

Asia WGS AF: 0.332 AC: 1151 AN: 3470

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	-0.48
CADD	Benign	15
DANN	Benign	0.70
PhyloP100		2.0
PromoterAI		-0.0060	Neutral
Mutation Taster		=299/1	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: rs3756132; hg19: chr4-71062256; COSMIC: COSV68573005; COSMIC: COSV68573005;