rs76469730

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_182981.3(OSGIN1):​c.516C>G​(p.Ala172Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,453,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

OSGIN1
NM_182981.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.89
Variant links:
Genes affected
OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]
NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP7
Synonymous conserved (PhyloP=-2.89 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OSGIN1NM_182981.3 linkc.516C>G p.Ala172Ala synonymous_variant Exon 6 of 6 ENST00000393306.6 NP_892026.1 Q9UJX0
NECAB2XM_047434240.1 linkc.-170C>G upstream_gene_variant XP_047290196.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OSGIN1ENST00000393306.6 linkc.516C>G p.Ala172Ala synonymous_variant Exon 6 of 6 1 NM_182981.3 ENSP00000376983.1 Q9UJX0
OSGIN1ENST00000361711.7 linkc.516C>G p.Ala172Ala synonymous_variant Exon 6 of 6 2 ENSP00000355374.3 Q9UJX0
OSGIN1ENST00000343939.6 linkn.1148C>G non_coding_transcript_exon_variant Exon 7 of 7 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000894
AC:
13
AN:
1453566
Hom.:
0
Cov.:
34
AF XY:
0.00000970
AC XY:
7
AN XY:
721588
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000994
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.023
DANN
Benign
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-83998694; API