rs10916293

Positions:

• chr1-228244229-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSCN	NM_001386125.1	c.3482-67C>T		intron_variant		ENST00000680850.1
OBSCN	NM_001098623.2	c.3206-67C>T		intron_variant
OBSCN	NM_001271223.3	c.3482-67C>T		intron_variant
OBSCN	NM_052843.4	c.3206-67C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSCN	ENST00000680850.1	c.3482-67C>T		intron_variant			NM_001386125.1	P4
	ENST00000664490.1	n.1659-4459G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.650

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

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.664

Alfa AF: 0.668 Hom.: 35379

Bravo AF: 0.677

Asia WGS AF: 0.526 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs10916293; hg19: chr1-228431930; COSMIC: COSV52754650;