1-228211781-C-G

Variant names:

• chr1-228211781-C-G
• rs11804508
• NM_001386125.1:c.-3C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001386125.1(OBSCN):​c.-3C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,523,938 control chromosomes in the GnomAD database, including 300,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31629 hom., cov: 30)
  • Exomes 𝑓: 0.62 (269285 hom.)
• Consequence: OBSCN NM_001386125.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.868
• Publications: 13 publications found

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]

OBSCN-AS1 (HGNC:32047): (OBSCN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-228211781-C-G is Benign according to our data. Variant chr1-228211781-C-G is described in ClinVar as Benign. ClinVar VariationId is 1272669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386125.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSCN	NM_001386125.1	MANE Select	c.-3C>G		5_prime_UTR	Exon 2 of 116	NP_001373054.1	Q5VST9-7
	OBSCN	NM_001271223.3		c.-3C>G		5_prime_UTR	Exon 2 of 116	NP_001258152.2
	OBSCN	NM_001098623.2		c.-3C>G		5_prime_UTR	Exon 2 of 105	NP_001092093.2	A0ABB0I190

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSCN	ENST00000680850.1	MANE Select	c.-3C>G		5_prime_UTR	Exon 2 of 116	ENSP00000505517.1	Q5VST9-7
	OBSCN-AS1	ENST00000295012.5	TSL:1	n.239+1641G>C		intron	N/A
	OBSCN	ENST00000570156.7	TSL:5	c.-3C>G		5_prime_UTR	Exon 2 of 116	ENSP00000455507.2	A6NGQ3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97392 AN: 151654 Hom.: 31593 Cov.: 30

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.648 AC: 112597 AN: 173808 AF XY: 0.651

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.598

Gnomad EAS exome AF: 0.824

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.640

GnomAD4 exome AF: 0.624 AC: 856341 AN: 1372166 Hom.: 269285 Cov.: 55 AF XY: 0.628 AC XY: 421964 AN XY: 672004

African (AFR) AF: 0.674 AC: 20878 AN: 30986

American (AMR) AF: 0.610 AC: 20745 AN: 34026

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 12645 AN: 21010

East Asian (EAS) AF: 0.837 AC: 32181 AN: 38440

South Asian (SAS) AF: 0.761 AC: 55653 AN: 73138

European-Finnish (FIN) AF: 0.651 AC: 31263 AN: 48022

Middle Eastern (MID) AF: 0.690 AC: 2766 AN: 4008

European-Non Finnish (NFE) AF: 0.604 AC: 644165 AN: 1066228

Other (OTH) AF: 0.640 AC: 36045 AN: 56308

GnomAD4 genome AF: 0.642 AC: 97479 AN: 151772 Hom.: 31629 Cov.: 30 AF XY: 0.650 AC XY: 48208 AN XY: 74198

African (AFR) AF: 0.656 AC: 27137 AN: 41388

American (AMR) AF: 0.633 AC: 9658 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2119 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4263 AN: 5062

South Asian (SAS) AF: 0.776 AC: 3737 AN: 4814

European-Finnish (FIN) AF: 0.662 AC: 7012 AN: 10588

Middle Eastern (MID) AF: 0.703 AC: 204 AN: 290

European-Non Finnish (NFE) AF: 0.610 AC: 41378 AN: 67874

Other (OTH) AF: 0.638 AC: 1345 AN: 2108

Alfa AF: 0.513 Hom.: 1613

Bravo AF: 0.639

Asia WGS AF: 0.815 AC: 2832 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		-0.87
PromoterAI		0.030	Neutral
Mutation Taster		=139/161	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11804508; hg19: chr1-228399482;