chr1-228295668-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386125.1(OBSCN):​c.12946+625C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,016 control chromosomes in the GnomAD database, including 41,477 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 0.73 ( 41477 hom., cov: 32)

Consequence

OBSCN
NM_001386125.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

2 publications found
Variant links:
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 Gene-Disease associations (from GenCC):
  • rhabdomyolysis, susceptibility to, 1
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OBSCNNM_001386125.1 linkc.12946+625C>T intron_variant Intron 48 of 115 ENST00000680850.1 NP_001373054.1
OBSCNNM_001271223.3 linkc.12946+625C>T intron_variant Intron 48 of 115 NP_001258152.2 A6NGQ3
OBSCNNM_001098623.2 linkc.11659+625C>T intron_variant Intron 43 of 104 NP_001092093.2 Q5VST9-1
OBSCNNM_052843.4 linkc.11659+625C>T intron_variant Intron 43 of 80 NP_443075.3 Q5VST9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OBSCNENST00000680850.1 linkc.12946+625C>T intron_variant Intron 48 of 115 NM_001386125.1 ENSP00000505517.1 A0A7P0Z489

Frequencies

GnomAD3 genomes
AF:
0.734
AC:
111567
AN:
151896
Hom.:
41437
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.824
Gnomad AMI
AF:
0.618
Gnomad AMR
AF:
0.729
Gnomad ASJ
AF:
0.646
Gnomad EAS
AF:
0.735
Gnomad SAS
AF:
0.502
Gnomad FIN
AF:
0.774
Gnomad MID
AF:
0.627
Gnomad NFE
AF:
0.699
Gnomad OTH
AF:
0.717
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.735
AC:
111662
AN:
152016
Hom.:
41477
Cov.:
32
AF XY:
0.733
AC XY:
54495
AN XY:
74298
show subpopulations
African (AFR)
AF:
0.824
AC:
34166
AN:
41480
American (AMR)
AF:
0.729
AC:
11135
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.646
AC:
2241
AN:
3468
East Asian (EAS)
AF:
0.734
AC:
3788
AN:
5158
South Asian (SAS)
AF:
0.503
AC:
2426
AN:
4820
European-Finnish (FIN)
AF:
0.774
AC:
8164
AN:
10552
Middle Eastern (MID)
AF:
0.629
AC:
185
AN:
294
European-Non Finnish (NFE)
AF:
0.699
AC:
47490
AN:
67942
Other (OTH)
AF:
0.712
AC:
1505
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1512
3024
4536
6048
7560
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
838
1676
2514
3352
4190
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.717
Hom.:
13154
Bravo
AF:
0.736
Asia WGS
AF:
0.605
AC:
2107
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
0.37
DANN
Benign
0.22
PhyloP100
-1.3
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs564636; hg19: chr1-228483369; API