rs287614

Positions:

• chr1-228301400-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSCN	NM_001386125.1	c.13738+1255C>A		intron_variant		ENST00000680850.1
OBSCN	NM_001098623.2	c.11660-4972C>A		intron_variant
OBSCN	NM_001271223.3	c.13738+1255C>A		intron_variant
OBSCN	NM_052843.4	c.11660-4972C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSCN	ENST00000680850.1	c.13738+1255C>A		intron_variant			NM_001386125.1	P4
	ENST00000602778.2	n.614+989G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

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

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.437

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.79

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