rs4782866

Variant names:

• chr16-83951520-A-G
• rs4782866
• ENST00000361711.7:c.-33+2014A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-83951520-A-G
• chr16-83951520-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361711.7(OSGIN1):​c.-33+2014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 458,028 control chromosomes in the GnomAD database, including 84,222 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 (25694 hom., cov: 31)
  • Exomes 𝑓: 0.61 (58528 hom.)
• Consequence: OSGIN1 ENST00000361711.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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]

MLYCD (HGNC:7150): (malonyl-CoA decarboxylase) The product of this gene catalyzes the breakdown of malonyl-CoA to acetyl-CoA and carbon dioxide. Malonyl-CoA is an intermediate in fatty acid biosynthesis, and also inhibits the transport of fatty acyl CoAs into mitochondria. Consequently, the encoded protein acts to increase the rate of fatty acid oxidation. It is found in mitochondria, peroxisomes, and the cytoplasm. Mutations in this gene result in malonyl-CoA decarboyxlase deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN1	ENST00000361711.7	c.-33+2014A>G		intron_variant	Intron 1 of 5	2		ENSP00000355374.3
OSGIN1	ENST00000343939.6	n.600+233A>G		intron_variant	Intron 2 of 6	2
OSGIN1	ENST00000566667.2	n.494-1742A>G		intron_variant	Intron 5 of 6	3
MLYCD	ENST00000561562.5	c.*272A>G		downstream_gene_variant		2		ENSP00000484042.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87045 AN: 151862 Hom.: 25688 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.613 AC: 187668 AN: 306048 Hom.: 58528 AF XY: 0.612 AC XY: 96629 AN XY: 157908

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.598

GnomAD4 genome AF: 0.573 AC: 87087 AN: 151980 Hom.: 25694 Cov.: 31 AF XY: 0.579 AC XY: 43041 AN XY: 74292

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.577

Alfa AF: 0.597 Hom.: 12338

Bravo AF: 0.562

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs4782866; hg19: chr16-83985125;