Genetic Variant OBSL1:c.5684-153C>T (chr2-219550995-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015311.3(OBSL1):c.5684-153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,496,186 control chromosomes in the GnomAD database, including 217,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18637 hom., cov: 32)

Exomes 𝑓: 0.54 ( 198680 hom. )

Consequence

OBSL1
NM_015311.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.704

Variant links:

Genes affected

OBSL1 (HGNC:29092): (obscurin like cytoskeletal adaptor 1) Cytoskeletal adaptor proteins function in linking the internal cytoskeleton of cells to the cell membrane. This gene encodes a cytoskeletal adaptor protein, which is a member of the Unc-89/obscurin family. The protein contains multiple N- and C-terminal immunoglobulin (Ig)-like domains and a central fibronectin type 3 domain. Mutations in this gene cause 3M syndrome type 2. Alternatively spliced transcript variants encoding different isoforms have been found in this gene. [provided by RefSeq, Mar 2010]

OBSL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-219550995-G-A is Benign according to our data. Variant chr2-219550995-G-A is described in ClinVar as [Benign]. Clinvar id is 1296814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSL1	NM_015311.3 link	c.5684-153C>T		intron_variant	Intron 20 of 20	ENST00000404537.6	NP_056126.1	O75147-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSL1	ENST00000404537.6 link	c.5684-153C>T		intron_variant	Intron 20 of 20	1	NM_015311.3	ENSP00000385636.1		O75147-3

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73332

AN:

151802

Hom.:

18631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.539

AC:

724595

AN:

1344266

Hom.:

198680

Cov.:

AF XY:

0.546

AC XY:

359507

AN XY:

658624

show subpopulations

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.738

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.528

Gnomad4 OTH exome

AF:

0.548

GnomAD4 genome

AF:

0.483

AC:

73360

AN:

151920

Hom.:

18637

Cov.:

AF XY:

0.484

AC XY:

35887

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.592

Gnomad4 SAS

AF:

0.746

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.539

Hom.:

10272

Bravo

AF:

0.474

Asia WGS

AF:

0.664

AC:

2302

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.9

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over