rs2761680

Variant names:

• chr9-92419851-G-C
• rs2761680
• NM_005014.3:c.-16-2277C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005014.3(OMD):​c.-16-2277C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,214 control chromosomes in the GnomAD database, including 60,559 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 0.89 (60559 hom., cov: 32)
• Consequence: OMD NM_005014.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 4 publications found

Genes affected

OMD (HGNC:8134): (osteomodulin) Predicted to be involved in cell adhesion and regulation of bone mineralization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OMD	NM_005014.3	c.-16-2277C>G		intron_variant	Intron 1 of 2	ENST00000375550.5	NP_005005.1
CENPP	NM_001012267.3	c.564+39992G>C		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMD	ENST00000375550.5	c.-16-2277C>G		intron_variant	Intron 1 of 2	1	NM_005014.3	ENSP00000364700.4
CENPP	ENST00000375587.8	c.564+39992G>C		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135504 AN: 152096 Hom.: 60512 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.891 AC: 135607 AN: 152214 Hom.: 60559 Cov.: 32 AF XY: 0.886 AC XY: 65902 AN XY: 74398

African (AFR) AF: 0.944 AC: 39232 AN: 41552

American (AMR) AF: 0.845 AC: 12911 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3203 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4911 AN: 5174

South Asian (SAS) AF: 0.788 AC: 3798 AN: 4818

European-Finnish (FIN) AF: 0.836 AC: 8854 AN: 10586

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59688 AN: 68006

Other (OTH) AF: 0.894 AC: 1889 AN: 2112

Alfa AF: 0.882 Hom.: 7359

Bravo AF: 0.896

Asia WGS AF: 0.887 AC: 3085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		-0.76
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: rs2761680; hg19: chr9-95182133;