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GeneBe

12-57694302-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006812.4(OS9):c.141G>A(p.Pro47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,614,124 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 41 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 40 hom. )

Consequence

OS9
NM_006812.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-57694302-G-A is Benign according to our data. Variant chr12-57694302-G-A is described in ClinVar as [Benign]. Clinvar id is 781084.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.223 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2035/152250) while in subpopulation AFR AF= 0.0466 (1937/41532). AF 95% confidence interval is 0.0449. There are 41 homozygotes in gnomad4. There are 964 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 41 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OS9NM_006812.4 linkuse as main transcriptc.141G>A p.Pro47= synonymous_variant 1/15 ENST00000315970.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OS9ENST00000315970.12 linkuse as main transcriptc.141G>A p.Pro47= synonymous_variant 1/151 NM_006812.4 P4Q13438-1
ENST00000549477.1 linkuse as main transcriptn.535-6C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0134
AC:
2033
AN:
152132
Hom.:
41
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0467
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00352
AC:
885
AN:
251442
Hom.:
16
AF XY:
0.00277
AC XY:
376
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.0489
Gnomad AMR exome
AF:
0.00142
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00135
AC:
1973
AN:
1461874
Hom.:
40
Cov.:
31
AF XY:
0.00119
AC XY:
868
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0487
Gnomad4 AMR exome
AF:
0.00165
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000603
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.00262
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0134
AC:
2035
AN:
152250
Hom.:
41
Cov.:
32
AF XY:
0.0130
AC XY:
964
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0466
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00606
Hom.:
12
Bravo
AF:
0.0153
Asia WGS
AF:
0.00144
AC:
6
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
12
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs34299538; hg19: chr12-58088085; API