Variant 1-228211781-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001386125.1(OBSCN):c.-3C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,523,938 control chromosomes in the GnomAD database, including 300,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31629 hom., cov: 30)

Exomes 𝑓: 0.62 ( 269285 hom. )

Consequence

OBSCN
NM_001386125.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.868

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:

OBSCN-AS1 (HGNC:):

OBSCN-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-228211781-C-G is Benign according to our data. Variant chr1-228211781-C-G is described in ClinVar as [Benign]. Clinvar id is 1272669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBSCN	NM_001386125.1 linkuse as main transcript	c.-3C>G		5_prime_UTR_variant	2/116	ENST00000680850.1	NP_001373054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850 linkuse as main transcript	c.-3C>G		5_prime_UTR_variant	2/116		NM_001386125.1	ENSP00000505517.1		A0A7P0Z489

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97392

AN:

151654

Hom.:

31593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.842

Gnomad SAS

AF:

0.777

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.633

GnomAD3 exomes

AF:

0.648

AC:

112597

AN:

173808

Hom.:

36962

AF XY:

0.651

AC XY:

61231

AN XY:

94000

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.824

Gnomad SAS exome

AF:

0.770

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.640

GnomAD4 exome

AF:

0.624

AC:

856341

AN:

1372166

Hom.:

269285

Cov.:

AF XY:

0.628

AC XY:

421964

AN XY:

672004

show subpopulations

Gnomad4 AFR exome

AF:

0.674

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.837

Gnomad4 SAS exome

AF:

0.761

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.604

Gnomad4 OTH exome

AF:

0.640

GnomAD4 genome

AF:

0.642

AC:

97479

AN:

151772

Hom.:

31629

Cov.:

AF XY:

0.650

AC XY:

48208

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.633

Gnomad4 ASJ

AF:

0.610

Gnomad4 EAS

AF:

0.842

Gnomad4 SAS

AF:

0.776

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.513

Hom.:

1613

Bravo

AF:

0.639

Asia WGS

AF:

0.815

AC:

2832

AN:

3476

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	GeneDx	Dec 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.37

Position offset: -21

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