dbSNP rs287614: OBSCN:c.13738+1255C>A (chr1-228301400-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386125.1(OBSCN):c.13738+1255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,058 control chromosomes in the GnomAD database, including 16,647 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 0.46 ( 16645 hom., cov: 33)

Exomes 𝑓: 0.63 ( 2 hom. )

Consequence

OBSCN
NM_001386125.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

rhabdomyolysis, susceptibility to, 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

OBSCN links:

ENSG00000270110 (HGNC:58608):

ENSG00000270110 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OBSCN	NM_001386125.1 link	c.13738+1255C>A	intron_variant	Intron 51 of 115	ENST00000680850.1	NP_001373054.1
OBSCN	NM_001271223.3 link	c.13738+1255C>A	intron_variant	Intron 51 of 115		NP_001258152.2	A6NGQ3
OBSCN	NM_001098623.2 link	c.11660-4972C>A	intron_variant	Intron 43 of 104		NP_001092093.2	Q5VST9-1
OBSCN	NM_052843.4 link	c.11660-4972C>A	intron_variant	Intron 43 of 80		NP_443075.3	Q5VST9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850.1 link	c.13738+1255C>A		intron_variant	Intron 51 of 115		NM_001386125.1	ENSP00000505517.1		A0A7P0Z489

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70263

AN:

151932

Hom.:

16640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.442

GnomAD4 exome

AF:

0.625

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.462

AC:

70283

AN:

152050

Hom.:

16645

Cov.:

AF XY:

0.462

AC XY:

34366

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.426

AC:

17664

AN:

41440

American (AMR)

AF:

0.435

AC:

6641

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1435

AN:

3470

East Asian (EAS)

AF:

0.225

AC:

1165

AN:

5174

South Asian (SAS)

AF:

0.320

AC:

1541

AN:

4812

European-Finnish (FIN)

AF:

0.571

AC:

6040

AN:

10576

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.506

AC:

34370

AN:

67984

Other (OTH)

AF:

0.437

AC:

924

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1940

3880

5821

7761

9701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.489

Hom.:

2948

Bravo

AF:

0.445

Asia WGS

AF:

0.277

AC:

969

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

(source)

DANN

Benign

0.79

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over