rs378090

chr1-228309769-A-Gchr1-228309769-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386125.1(OBSCN):c.15883+210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,104 control chromosomes in the GnomAD database, including 41,771 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 0.74 (41771 hom., cov: 32)
• Consequence: OBSCN NM_001386125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSCN	NM_001386125.1	c.15883+210A>G		intron_variant		ENST00000680850.1
OBSCN	NM_001098623.2	c.13012+210A>G		intron_variant
OBSCN	NM_001271223.3	c.15883+210A>G		intron_variant
OBSCN	NM_052843.4	c.13012+210A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSCN	ENST00000680850.1	c.15883+210A>G		intron_variant			NM_001386125.1	P4

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111967 AN: 151986 Hom.: 41728 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 112063 AN: 152104 Hom.: 41771 Cov.: 32 AF XY: 0.736 AC XY: 54688 AN XY: 74342

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.713

Alfa AF: 0.729 Hom.: 6891

Bravo AF: 0.739

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.3
Dann	Benign	0.58

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: rs378090; hg19: chr1-228497470; COSMIC: COSV52848187;