rs564636

Variant names:

• chr1-228295668-C-T
• rs564636
• NM_001386125.1:c.12946+625C>T

Variant summary

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

The NM_001386125.1(OBSCN):​c.12946+625C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,016 control chromosomes in the GnomAD database, including 41,477 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 0.73 (41477 hom., cov: 32)
• Consequence: OBSCN NM_001386125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 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.12946+625C>T		intron	N/A	NP_001373054.1	Q5VST9-7
	OBSCN	NM_001271223.3		c.12946+625C>T		intron	N/A	NP_001258152.2
	OBSCN	NM_001098623.2		c.11659+625C>T		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.12946+625C>T		intron	N/A	ENSP00000505517.1	Q5VST9-7
	OBSCN	ENST00000636476.2	TSL:1	c.11659+625C>T		intron	N/A	ENSP00000489816.2	A0ABB0L580
	OBSCN	ENST00000570156.7	TSL:5	c.12946+625C>T		intron	N/A	ENSP00000455507.2	A6NGQ3

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111567 AN: 151896 Hom.: 41437 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.717

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.735 AC: 111662 AN: 152016 Hom.: 41477 Cov.: 32 AF XY: 0.733 AC XY: 54495 AN XY: 74298

African (AFR) AF: 0.824 AC: 34166 AN: 41480

American (AMR) AF: 0.729 AC: 11135 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3788 AN: 5158

South Asian (SAS) AF: 0.503 AC: 2426 AN: 4820

European-Finnish (FIN) AF: 0.774 AC: 8164 AN: 10552

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47490 AN: 67942

Other (OTH) AF: 0.712 AC: 1505 AN: 2114

Alfa AF: 0.717 Hom.: 13154

Bravo AF: 0.736

Asia WGS AF: 0.605 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.22
PhyloP100		-1.3
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: rs564636; hg19: chr1-228483369;