rs1150910

Variant names:

• chr1-228304343-G-A
• rs1150910
• NM_001386125.1:c.14043G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001386125.1(OBSCN):​c.14043G>A​(p.Glu4681Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,612,892 control chromosomes in the GnomAD database, including 186,049 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 0.45 (15812 hom., cov: 31)
  • Exomes 𝑓: 0.48 (170237 hom.)
• Consequence: OBSCN NM_001386125.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 12 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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.
• 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.14043G>A	p.Glu4681Glu	synonymous	Exon 53 of 116	NP_001373054.1	Q5VST9-7
	OBSCN	NM_001271223.3		c.14043G>A	p.Glu4681Glu	synonymous	Exon 53 of 116	NP_001258152.2
	OBSCN	NM_001098623.2		c.11660-2029G>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.14043G>A	p.Glu4681Glu	synonymous	Exon 53 of 116	ENSP00000505517.1	Q5VST9-7
	OBSCN	ENST00000636476.2	TSL:1	c.11660-2029G>A		intron	N/A	ENSP00000489816.2	A0ABB0L580
	OBSCN	ENST00000570156.7	TSL:5	c.14043G>A	p.Glu4681Glu	synonymous	Exon 53 of 116	ENSP00000455507.2	A6NGQ3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68188 AN: 151734 Hom.: 15809 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.433

GnomAD2 exomes AF: 0.430 AC: 106560 AN: 248030 AF XY: 0.430

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.478 AC: 697896 AN: 1461040 Hom.: 170237 Cov.: 52 AF XY: 0.473 AC XY: 343533 AN XY: 726734

African (AFR) AF: 0.378 AC: 12663 AN: 33464

American (AMR) AF: 0.375 AC: 16739 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 10854 AN: 26110

East Asian (EAS) AF: 0.232 AC: 9189 AN: 39690

South Asian (SAS) AF: 0.334 AC: 28842 AN: 86228

European-Finnish (FIN) AF: 0.555 AC: 29596 AN: 53318

Middle Eastern (MID) AF: 0.337 AC: 1943 AN: 5766

European-Non Finnish (NFE) AF: 0.505 AC: 560979 AN: 1111470

Other (OTH) AF: 0.449 AC: 27091 AN: 60342

GnomAD4 genome AF: 0.449 AC: 68207 AN: 151852 Hom.: 15812 Cov.: 31 AF XY: 0.449 AC XY: 33330 AN XY: 74186

African (AFR) AF: 0.382 AC: 15823 AN: 41386

American (AMR) AF: 0.427 AC: 6517 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1430 AN: 3466

East Asian (EAS) AF: 0.226 AC: 1161 AN: 5138

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4806

European-Finnish (FIN) AF: 0.571 AC: 6021 AN: 10550

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34311 AN: 67914

Other (OTH) AF: 0.428 AC: 904 AN: 2112

Alfa AF: 0.475 Hom.: 44578

Bravo AF: 0.430

Asia WGS AF: 0.275 AC: 962 AN: 3478

EpiCase AF: 0.481

EpiControl AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.4
DANN	Benign	0.52
PhyloP100		0.068
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: rs1150910; hg19: chr1-228492044; COSMIC: COSV52741432; COSMIC: COSV52741432;