12-57695630-A-T

Variant names:

• chr12-57695630-A-T
• rs3825078
• NM_006812.4:c.340-150A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006812.4(OS9):​c.340-150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 722,874 control chromosomes in the GnomAD database, including 132,211 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 0.57 (26037 hom., cov: 31)
  • Exomes 𝑓: 0.60 (106174 hom.)
• Consequence: OS9 NM_006812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 18 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OS9	NM_006812.4	c.340-150A>T		intron_variant	Intron 2 of 14	ENST00000315970.12	NP_006803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OS9	ENST00000315970.12	c.340-150A>T		intron_variant	Intron 2 of 14	1	NM_006812.4	ENSP00000318165.7

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87212 AN: 151804 Hom.: 26042 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.597 AC: 340795 AN: 570950 Hom.: 106174 Cov.: 4 AF XY: 0.587 AC XY: 181581 AN XY: 309156

African (AFR) AF: 0.421 AC: 6741 AN: 16024

American (AMR) AF: 0.619 AC: 21744 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 13563 AN: 20082

East Asian (EAS) AF: 0.285 AC: 9263 AN: 32542

South Asian (SAS) AF: 0.394 AC: 25084 AN: 63650

European-Finnish (FIN) AF: 0.612 AC: 28757 AN: 47026

Middle Eastern (MID) AF: 0.626 AC: 2555 AN: 4084

European-Non Finnish (NFE) AF: 0.666 AC: 214158 AN: 321450

Other (OTH) AF: 0.611 AC: 18930 AN: 30964

GnomAD4 genome AF: 0.574 AC: 87234 AN: 151924 Hom.: 26037 Cov.: 31 AF XY: 0.567 AC XY: 42108 AN XY: 74268

African (AFR) AF: 0.429 AC: 17761 AN: 41388

American (AMR) AF: 0.634 AC: 9684 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3466

East Asian (EAS) AF: 0.350 AC: 1803 AN: 5156

South Asian (SAS) AF: 0.387 AC: 1869 AN: 4824

European-Finnish (FIN) AF: 0.595 AC: 6279 AN: 10546

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45520 AN: 67964

Other (OTH) AF: 0.625 AC: 1313 AN: 2100

Alfa AF: 0.488 Hom.: 1418

Bravo AF: 0.573

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3825078; hg19: chr12-58089413; COSMIC: COSV104382034; COSMIC: COSV104382034;