1-228344451-T-G

Variant names:

• chr1-228344451-T-G
• rs369252
• NM_001386125.1:c.21019+2219T>G

Variant summary

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

The NM_001386125.1(OBSCN):​c.21019+2219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,202 control chromosomes in the GnomAD database, including 42,300 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 (42300 hom., cov: 35)
• Consequence: OBSCN NM_001386125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSCN	NM_001386125.1	c.21019+2219T>G		intron_variant	Intron 86 of 115	ENST00000680850.1	NP_001373054.1
OBSCN	NM_001271223.3	c.21019+2219T>G		intron_variant	Intron 86 of 115		NP_001258152.2
OBSCN	NM_001098623.2	c.18148+2219T>G		intron_variant	Intron 75 of 104		NP_001092093.2
OBSCN	NM_052843.4	c.18148+2219T>G		intron_variant	Intron 75 of 80		NP_443075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850.1	c.21019+2219T>G		intron_variant	Intron 86 of 115		NM_001386125.1	ENSP00000505517.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112655 AN: 152084 Hom.: 42252 Cov.: 35

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.741 AC: 112756 AN: 152202 Hom.: 42300 Cov.: 35 AF XY: 0.740 AC XY: 55079 AN XY: 74406

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.714

Alfa AF: 0.733 Hom.: 5111

Bravo AF: 0.742

Asia WGS AF: 0.616 AC: 2144 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	0.77
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs369252; hg19: chr1-228532152;