Variant 12-57696268-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006812.4(OS9):c.481-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,603,764 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 43 hom., cov: 31)

Exomes 𝑓: 0.0070 ( 79 hom. )

Consequence

OS9
NM_006812.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003254

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.261

Variant links:

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]

OS9 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-57696268-T-C is Benign according to our data. Variant chr12-57696268-T-C is described in ClinVar as [Benign]. Clinvar id is 776728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0171 (2609/152216) while in subpopulation AFR AF= 0.0431 (1791/41518). AF 95% confidence interval is 0.0415. There are 43 homozygotes in gnomad4. There are 1216 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OS9	NM_006812.4 linkuse as main transcript	c.481-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000315970.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OS9	ENST00000315970.12 linkuse as main transcript	c.481-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006812.4	P4	Q13438-1
	ENST00000549477.1 linkuse as main transcript	n.535-1972A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2609

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0432

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00830

AC:

2043

AN:

246192

Hom.:

AF XY:

0.00750

AC XY:

999

AN XY:

133198

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.00675

Gnomad ASJ exome

AF:

0.00477

Gnomad EAS exome

AF:

0.00412

Gnomad SAS exome

AF:

0.00335

Gnomad FIN exome

AF:

0.00266

Gnomad NFE exome

AF:

0.00682

Gnomad OTH exome

AF:

0.00754

GnomAD4 exome

AF:

0.00702

AC:

10197

AN:

1451548

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4881

AN XY:

722110

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.00796

Gnomad4 ASJ exome

AF:

0.00435

Gnomad4 EAS exome

AF:

0.00250

Gnomad4 SAS exome

AF:

0.00313

Gnomad4 FIN exome

AF:

0.00295

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00912

GnomAD4 genome

AF:

0.0171

AC:

2609

AN:

152216

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1216

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00406

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.7

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over