rs1039900

chr2-219559765-G-Achr2-219559765-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015311.3(OBSL1):c.2954-268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 461,726 control chromosomes in the GnomAD database, including 45,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (16998 hom., cov: 32)
  • Exomes 𝑓: 0.41 (28165 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-219559765-G-A is Benign according to our data. Variant chr2-219559765-G-A is described in ClinVar as [Benign]. Clinvar id is 1283559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSL1	NM_015311.3	c.2954-268C>T		intron_variant		ENST00000404537.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSL1	ENST00000404537.6	c.2954-268C>T		intron_variant		1	NM_015311.3	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70859 AN: 151738 Hom.: 16981 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.415 AC: 128518 AN: 309872 Hom.: 28165 AF XY: 0.407 AC XY: 64822 AN XY: 159418

Gnomad4 AFR exome AF: 0.528

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.467 AC: 70917 AN: 151854 Hom.: 16998 Cov.: 32 AF XY: 0.464 AC XY: 34477 AN XY: 74226

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.430

Alfa AF: 0.407 Hom.: 2505

Bravo AF: 0.476

Asia WGS AF: 0.322 AC: 1129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.2
Dann	Benign	0.50

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: rs1039900; hg19: chr2-220424487;