8-89914707-C-T

Variant names:

• chr8-89914707-C-T
• rs77303215
• NM_001126111.3:c.489C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001126111.3(OSGIN2):​c.489C>T​(p.His163His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,613,910 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (53 hom.)
• Consequence: OSGIN2 NM_001126111.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109
• Publications: 1 publications found

Genes affected

OSGIN2 (HGNC:1355): (oxidative stress induced growth inhibitor family member 2) Predicted to enable growth factor activity. Predicted to be involved in negative regulation of cell growth. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 8-89914707-C-T is Benign according to our data. Variant chr8-89914707-C-T is described in ClinVar as Benign. ClinVar VariationId is 784133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.109 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN2	NM_001126111.3	MANE Select	c.489C>T	p.His163His	synonymous	Exon 4 of 6	NP_001119583.1	Q9Y236-2
	OSGIN2	NM_004337.2		c.357C>T	p.His119His	synonymous	Exon 4 of 6	NP_004328.1	Q9Y236-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN2	ENST00000451899.7	TSL:1 MANE Select	c.489C>T	p.His163His	synonymous	Exon 4 of 6	ENSP00000396445.2	Q9Y236-2
	OSGIN2	ENST00000297438.6	TSL:1	c.357C>T	p.His119His	synonymous	Exon 4 of 6	ENSP00000297438.2	Q9Y236-1
	OSGIN2	ENST00000869563.1		c.447C>T	p.His149His	synonymous	Exon 4 of 6	ENSP00000539622.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2447 AN: 152190 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00379 AC: 952 AN: 251294 AF XY: 0.00270

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00148 AC: 2157 AN: 1461602 Hom.: 53 Cov.: 31 AF XY: 0.00128 AC XY: 934 AN XY: 727110

African (AFR) AF: 0.0551 AC: 1844 AN: 33462

American (AMR) AF: 0.00264 AC: 118 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111772

Other (OTH) AF: 0.00270 AC: 163 AN: 60390

GnomAD4 genome AF: 0.0161 AC: 2455 AN: 152308 Hom.: 64 Cov.: 32 AF XY: 0.0155 AC XY: 1151 AN XY: 74488

African (AFR) AF: 0.0562 AC: 2338 AN: 41566

American (AMR) AF: 0.00614 AC: 94 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68030

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00742 Hom.: 21

Bravo AF: 0.0178

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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: rs77303215; hg19: chr8-90926935;