NM_001386125.1:c.3482-67C>T

Variant names:

• chr1-228244229-C-T
• rs10916293
• NM_001386125.1:c.3482-67C>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.3482-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,575,488 control chromosomes in the GnomAD database, including 351,705 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 0.68 (35068 hom., cov: 33)
  • Exomes 𝑓: 0.67 (316637 hom.)
• Consequence: OBSCN NM_001386125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 10 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

ENSG00000269934 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSCN	NM_001386125.1	MANE Select	c.3482-67C>T		intron	N/A	NP_001373054.1
	OBSCN	NM_001271223.3		c.3482-67C>T		intron	N/A	NP_001258152.2
	OBSCN	NM_001098623.2		c.3206-67C>T		intron	N/A	NP_001092093.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSCN	ENST00000680850.1	MANE Select	c.3482-67C>T		intron	N/A	ENSP00000505517.1
	OBSCN	ENST00000636476.2	TSL:1	c.3206-67C>T		intron	N/A	ENSP00000489816.2
	OBSCN	ENST00000570156.7	TSL:5	c.3482-67C>T		intron	N/A	ENSP00000455507.2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102935 AN: 151998 Hom.: 35028 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.665 AC: 946690 AN: 1423372 Hom.: 316637 AF XY: 0.659 AC XY: 463409 AN XY: 703102

African (AFR) AF: 0.705 AC: 23098 AN: 32780

American (AMR) AF: 0.681 AC: 29174 AN: 42836

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 15265 AN: 23834

East Asian (EAS) AF: 0.586 AC: 22996 AN: 39236

South Asian (SAS) AF: 0.503 AC: 40487 AN: 80488

European-Finnish (FIN) AF: 0.699 AC: 36327 AN: 51956

Middle Eastern (MID) AF: 0.560 AC: 3126 AN: 5586

European-Non Finnish (NFE) AF: 0.678 AC: 738053 AN: 1087934

Other (OTH) AF: 0.650 AC: 38164 AN: 58722

GnomAD4 genome AF: 0.677 AC: 103022 AN: 152116 Hom.: 35068 Cov.: 33 AF XY: 0.674 AC XY: 50125 AN XY: 74358

African (AFR) AF: 0.706 AC: 29262 AN: 41464

American (AMR) AF: 0.686 AC: 10501 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3472

East Asian (EAS) AF: 0.579 AC: 2991 AN: 5168

South Asian (SAS) AF: 0.504 AC: 2435 AN: 4830

European-Finnish (FIN) AF: 0.699 AC: 7391 AN: 10574

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46136 AN: 67988

Other (OTH) AF: 0.664 AC: 1404 AN: 2116

Alfa AF: 0.669 Hom.: 42215

Bravo AF: 0.677

Asia WGS AF: 0.526 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.41
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: rs10916293; hg19: chr1-228431930; COSMIC: COSV52754650;