rs287614

Variant names:

• chr1-228301400-C-A
• rs287614
• NM_001386125.1:c.13738+1255C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 3 publications found

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

ENSG00000270110 (HGNC:58608):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386125.1. 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
	OBSCN	NM_001386125.1	MANE Select	c.13738+1255C>A		intron	N/A	NP_001373054.1	Q5VST9-7
	OBSCN	NM_001271223.3		c.13738+1255C>A		intron	N/A	NP_001258152.2
	OBSCN	NM_001098623.2		c.11660-4972C>A		intron	N/A	NP_001092093.2	A0ABB0I190

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSCN	ENST00000680850.1	MANE Select	c.13738+1255C>A		intron	N/A	ENSP00000505517.1	Q5VST9-7
	OBSCN	ENST00000636476.2	TSL:1	c.11660-4972C>A		intron	N/A	ENSP00000489816.2	A0ABB0L580
	OBSCN	ENST00000483539.3	TSL:5	c.*1238C>A		3_prime_UTR	Exon 8 of 8	ENSP00000455688.3	H3BQA7

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70263 AN: 151932 Hom.: 16640 Cov.: 33

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: 5 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.462 AC: 70283 AN: 152050 Hom.: 16645 Cov.: 33 AF XY: 0.462 AC XY: 34366 AN XY: 74374

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs287614; hg19: chr1-228489101; COSMIC: COSV52755804; COSMIC: COSV52755804;