Variant 3-191218788-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_198184.2(OSTN):c.144A>G(p.Thr48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 1,614,078 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 32)

Exomes 𝑓: 0.010 ( 87 hom. )

Consequence

OSTN
NM_198184.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.234

Variant links:

Genes affected

OSTN (HGNC:29961): (osteocrin) Predicted to enable signaling receptor binding activity. Involved in negative regulation of dendrite extension. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

OSTN links:

OSTN-AS1 (HGNC:41250): (OSTN antisense RNA 1)

OSTN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-191218788-A-G is Benign according to our data. Variant chr3-191218788-A-G is described in ClinVar as [Benign]. Clinvar id is 775208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.234 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OSTN	NM_198184.2 linkuse as main transcript	c.144A>G	p.Thr48=	synonymous_variant	3/5	ENST00000682035.1	NP_937827.1
OSTN-AS1	NR_133663.1 linkuse as main transcript	n.355+28T>C		intron_variant, non_coding_transcript_variant
OSTN	XM_017006303.3 linkuse as main transcript	c.144A>G	p.Thr48=	synonymous_variant	3/5		XP_016861792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OSTN	ENST00000682035.1 linkuse as main transcript	c.144A>G	p.Thr48=	synonymous_variant	3/5		NM_198184.2	ENSP00000508312	P1
OSTN-AS1	ENST00000430375.1 linkuse as main transcript	n.355+28T>C		intron_variant, non_coding_transcript_variant		5
OSTN	ENST00000445281.5 linkuse as main transcript	c.144A>G	p.Thr48=	synonymous_variant	3/4	5		ENSP00000416576

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1068

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00470

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00906

AC:

2277

AN:

251198

Hom.:

AF XY:

0.00977

AC XY:

1326

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.00883

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00998

AC:

14584

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7299

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0143

Gnomad4 FIN exome

AF:

0.00827

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00701

AC:

1067

AN:

152306

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

539

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00470

Gnomad4 NFE

AF:

0.00910

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00895

Hom.:

Bravo

AF:

0.00749

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over