NM_006812.4:c.580-1491C>T

Variant names:

• chr12-57714269-C-T
• rs1633360
• NM_006812.4:c.580-1491C>T

Variant summary

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

The NM_006812.4(OS9):​c.580-1491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,972 control chromosomes in the GnomAD database, including 21,715 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 0.53 (21715 hom., cov: 32)
• Consequence: OS9 NM_006812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 19 publications found

Genes affected

OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000257342 (HGNC:58278):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OS9	NM_006812.4	c.580-1491C>T		intron_variant	Intron 5 of 14	ENST00000315970.12	NP_006803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OS9	ENST00000315970.12	c.580-1491C>T		intron_variant	Intron 5 of 14	1	NM_006812.4	ENSP00000318165.7

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80156 AN: 151854 Hom.: 21717 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.528 AC: 80182 AN: 151972 Hom.: 21715 Cov.: 32 AF XY: 0.523 AC XY: 38823 AN XY: 74270

African (AFR) AF: 0.422 AC: 17480 AN: 41436

American (AMR) AF: 0.602 AC: 9198 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2283 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1808 AN: 5160

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4816

European-Finnish (FIN) AF: 0.527 AC: 5555 AN: 10548

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40193 AN: 67950

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.551 Hom.: 2942

Bravo AF: 0.531

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.38
PhyloP100		-1.6
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: rs1633360; hg19: chr12-58108052;