2-219569323-T-C

Variant names:

• chr2-219569323-T-C
• rs3731920
• NM_015311.3:c.1012+898A>G

Variant summary

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

The NM_015311.3(OBSL1):​c.1012+898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,150 control chromosomes in the GnomAD database, including 51,704 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 0.81 (51700 hom., cov: 31)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

INHA (HGNC:6065): (inhibin subunit alpha) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate multiple peptide products, including the alpha subunit of the inhibin A and B protein complexes. These complexes negatively regulate follicle stimulating hormone secretion from the pituitary gland. Inhibins have also been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. Mutations in this gene may be associated with male infertility and premature ovarian failure in female human patients. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSL1	NM_015311.3	c.1012+898A>G		intron_variant	Intron 1 of 20	ENST00000404537.6	NP_056126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSL1	ENST00000404537.6	c.1012+898A>G		intron_variant	Intron 1 of 20	1	NM_015311.3	ENSP00000385636.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123743 AN: 152024 Hom.: 51670 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.838

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.814 AC: 123825 AN: 152142 Hom.: 51700 Cov.: 31 AF XY: 0.815 AC XY: 60640 AN XY: 74406

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.839

Alfa AF: 0.880 Hom.: 31534

Bravo AF: 0.799

Asia WGS AF: 0.856 AC: 2977 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.85

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: rs3731920; hg19: chr2-220434045;