rs2292016

Variant names:

• chr5-38845758-G-T
• rs2292016
• ENST00000512519.1:n.72C>A

Variant summary

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

The ENST00000512519.1(OSMR-DT):​n.72C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,724 control chromosomes in the GnomAD database, including 398 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 0.023 (397 hom., cov: 32)
  • Exomes 𝑓: 0.025 (1 hom.)
• Consequence: OSMR-DT ENST00000512519.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

OSMR-DT (HGNC:50296): (OSMR divergent transcript)

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR-DT	NR_109951.1	n.72C>A		non_coding_transcript_exon_variant	Exon 1 of 4
OSMR-DT	NR_171676.1	n.12C>A		non_coding_transcript_exon_variant	Exon 1 of 3
OSMR-DT	NR_171677.1	n.12C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR-DT	ENST00000512519.1	n.72C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
OSMR-DT	ENST00000513480.1	n.11C>A		non_coding_transcript_exon_variant	Exon 1 of 4	4
OSMR-DT	ENST00000636516.2	n.36C>A		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3493 AN: 152124 Hom.: 396 Cov.: 32

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0249 AC: 12 AN: 482 Hom.: 1 Cov.: 0 AF XY: 0.0265 AC XY: 10 AN XY: 378

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0229 AC: 3491 AN: 152242 Hom.: 397 Cov.: 32 AF XY: 0.0245 AC XY: 1820 AN XY: 74418

Gnomad4 AFR AF: 0.00447

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.00762

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0177 Hom.: 39

Bravo AF: 0.0255

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.4
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2292016; hg19: chr5-38845860;