rs435776

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001386125.1(OBSCN):c.14986G>A(p.Gly4996Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,613,582 control chromosomes in the GnomAD database, including 179,831 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 12840 hom., cov: 33)

Exomes 𝑓: 0.47 ( 166991 hom. )

Consequence

OBSCN
NM_001386125.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.596

Variant links:

Genes affected

OBSCN (HGNC:15719): (obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF) The obscurin gene spans more than 150 kb, contains over 80 exons and encodes a protein of approximately 720 kDa. The encoded protein contains 68 Ig domains, 2 fibronectin domains, 1 calcium/calmodulin-binding domain, 1 RhoGEF domain with an associated PH domain, and 2 serine-threonine kinase domains. This protein belongs to the family of giant sacromeric signaling proteins that includes titin and nebulin, and may have a role in the organization of myofibrils during assembly and may mediate interactions between the sarcoplasmic reticulum and myofibrils. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OBSCN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8668175E-4).

BP6

Variant 1-228307089-G-A is Benign according to our data. Variant chr1-228307089-G-A is described in ClinVar as [Benign]. Clinvar id is 3060499.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSCN	NM_001386125.1 link	c.14986G>A	p.Gly4996Arg	missense_variant	Exon 56 of 116	ENST00000680850.1	NP_001373054.1
OBSCN	NM_001271223.3 link	c.14986G>A	p.Gly4996Arg	missense_variant	Exon 56 of 116		NP_001258152.2	A6NGQ3
OBSCN	NM_001098623.2 link	c.12115G>A	p.Gly4039Arg	missense_variant	Exon 45 of 105		NP_001092093.2	Q5VST9-1
OBSCN	NM_052843.4 link	c.12115G>A	p.Gly4039Arg	missense_variant	Exon 45 of 81		NP_443075.3	Q5VST9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850.1 link	c.14986G>A	p.Gly4996Arg	missense_variant	Exon 56 of 116		NM_001386125.1	ENSP00000505517.1		A0A7P0Z489

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56382

AN:

151960

Hom.:

12838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.378

GnomAD3 exomes

AF:

0.410

AC:

101909

AN:

248620

Hom.:

23032

AF XY:

0.415

AC XY:

56004

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.469

AC:

686043

AN:

1461504

Hom.:

166991

Cov.:

AF XY:

0.466

AC XY:

338540

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0947

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.371

AC:

56387

AN:

152078

Hom.:

12840

Cov.:

AF XY:

0.373

AC XY:

27688

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.461

Hom.:

41027

Bravo

AF:

0.340

TwinsUK

AF:

0.510

AC:

1892

ALSPAC

AF:

0.505

AC:

1947

ESP6500AA

AF:

0.117

AC:

513

ESP6500EA

AF:

0.494

AC:

4232

ExAC

AF:

0.406

AC:

49236

Asia WGS

AF:

0.260

AC:

908

AN:

3478

EpiCase

AF:

0.480

EpiControl

AF:

0.476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

OBSCN-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.8

DANN

Benign

0.68

DEOGEN2

Benign

0.095

.;T;.;.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.56

T;T;T;.;.

MetaRNN

Benign

0.00019

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;L;.;.;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.2

N;N;.;.;.

REVEL

Benign

0.033

Sift

Benign

0.46

T;T;.;.;.

Sift4G

Benign

0.21

T;T;D;D;.

Polyphen

0.058

B;P;.;.;P

Vest4

0.18

MutPred

0.45

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;Loss of sheet (P = 0.0315);

MPC

0.50

ClinPred

0.012

GERP RS

0.34

Varity_R

0.049

gMVP

0.072

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

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