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. The variant received -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
• Publications: 7 publications found

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]

MLYCD Gene-Disease associations (from GenCC):

• malonic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361711.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN1	ENST00000361711.7	TSL:2	c.-33+2014A>G		intron	N/A	ENSP00000355374.3
	OSGIN1	ENST00000343939.6	TSL:2	n.600+233A>G		intron	N/A
	OSGIN1	ENST00000566667.2	TSL:3	n.494-1742A>G		intron	N/A

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

African (AFR) AF: 0.432 AC: 3460 AN: 8012

American (AMR) AF: 0.640 AC: 6605 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 5503 AN: 10404

East Asian (EAS) AF: 0.764 AC: 17088 AN: 22380

South Asian (SAS) AF: 0.576 AC: 11609 AN: 20162

European-Finnish (FIN) AF: 0.685 AC: 15028 AN: 21932

Middle Eastern (MID) AF: 0.565 AC: 824 AN: 1458

European-Non Finnish (NFE) AF: 0.604 AC: 116155 AN: 192314

Other (OTH) AF: 0.598 AC: 11396 AN: 19072

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

African (AFR) AF: 0.430 AC: 17829 AN: 41420

American (AMR) AF: 0.622 AC: 9502 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1873 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4045 AN: 5160

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4820

European-Finnish (FIN) AF: 0.697 AC: 7377 AN: 10584

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41562 AN: 67930

Other (OTH) AF: 0.577 AC: 1220 AN: 2114

Alfa AF: 0.597 Hom.: 13712

Bravo AF: 0.562

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.84
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4782866; hg19: chr16-83985125;