5-38881526-G-T

Variant summary

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

The NM_003999.3(OSMR):c.247-67G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,612,720 control chromosomes in the GnomAD database, including 45,318 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 0.27 (6005 hom., cov: 33)
  • Exomes 𝑓: 0.23 (39313 hom.)
• Consequence: OSMR NM_003999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

Genes affected

OSMR (HGNC:8507): (oncostatin M receptor) This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3	c.247-67G>T		intron_variant		ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8	c.247-67G>T		intron_variant		1	NM_003999.3	P1
OSMR	ENST00000502536.5	c.247-67G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40710 AN: 152016 Hom.: 6006 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.226 AC: 330290 AN: 1460586 Hom.: 39313 Cov.: 34 AF XY: 0.225 AC XY: 163781 AN XY: 726596

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.268 AC: 40729 AN: 152134 Hom.: 6005 Cov.: 33 AF XY: 0.268 AC XY: 19904 AN XY: 74372

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.246

Alfa AF: 0.224 Hom.: 7865

Bravo AF: 0.265

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.9
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs525735; hg19: chr5-38881628; COSMIC: COSV57094191;