chr1-228347383-C-T

Position:

• chr1-228347383-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.21020-2507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,010 control chromosomes in the GnomAD database, including 12,501 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 0.40 (12501 hom., cov: 32)
• Consequence: OBSCN NM_001386125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBSCN	NM_001386125.1	c.21020-2507C>T		intron_variant		ENST00000680850.1	NP_001373054.1
OBSCN	NM_001098623.2	c.18149-2507C>T		intron_variant			NP_001092093.2
OBSCN	NM_001271223.3	c.21020-2507C>T		intron_variant			NP_001258152.2
OBSCN	NM_052843.4	c.18149-2507C>T		intron_variant			NP_443075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850.1	c.21020-2507C>T		intron_variant			NM_001386125.1	ENSP00000505517	P4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60804 AN: 151894 Hom.: 12500 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.400 AC: 60827 AN: 152010 Hom.: 12501 Cov.: 32 AF XY: 0.399 AC XY: 29632 AN XY: 74340

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.385

Alfa AF: 0.425 Hom.: 2826

Bravo AF: 0.390

Asia WGS AF: 0.251 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.54

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: rs374400; hg19: chr1-228535084; COSMIC: COSV52756061;