rs1150910

chr1-228304343-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001386125.1(OBSCN):c.14043G>A(p.Glu4681=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSCN	NM_001386125.1	c.14043G>A	p.Glu4681=	synonymous_variant	53/116	ENST00000680850.1
OBSCN	NM_001271223.3	c.14043G>A	p.Glu4681=	synonymous_variant	53/116
OBSCN	NM_001098623.2	c.11660-2029G>A		intron_variant
OBSCN	NM_052843.4	c.11660-2029G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSCN	ENST00000680850.1	c.14043G>A	p.Glu4681=	synonymous_variant	53/116		NM_001386125.1	P4

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

GnomAD3 exomes AF: 0.430 AC: 106560 AN: 248030 Hom.: 24252 AF XY: 0.430 AC XY: 57907 AN XY: 134648

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 SAS exome AF: 0.328

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

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.449

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

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.428

Alfa AF: 0.476 Hom.: 29982

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	6.4
Dann	Benign	0.52

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: rs1150910; hg19: chr1-228492044; COSMIC: COSV52741432; COSMIC: COSV52741432;