chr5-38881526-G-T

Variant names:

• chr5-38881526-G-T
• rs525735
• NM_003999.3:c.247-67G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

OSMR Gene-Disease associations (from GenCC):

• amyloidosis, primary localized cutaneous, 1

  Inheritance: SD, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• familial primary localized cutaneous amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	NM_003999.3	MANE Select	c.247-67G>T		intron	N/A	NP_003990.1
	OSMR	NM_001323506.2		c.247-67G>T		intron	N/A	NP_001310435.1
	OSMR	NM_001323505.2		c.247-67G>T		intron	N/A	NP_001310434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	ENST00000274276.8	TSL:1 MANE Select	c.247-67G>T		intron	N/A	ENSP00000274276.3
	OSMR	ENST00000502536.5	TSL:1	c.247-67G>T		intron	N/A	ENSP00000422023.1

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

African (AFR) AF: 0.380 AC: 12699 AN: 33458

American (AMR) AF: 0.117 AC: 5243 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4957 AN: 26120

East Asian (EAS) AF: 0.374 AC: 14843 AN: 39666

South Asian (SAS) AF: 0.193 AC: 16613 AN: 85986

European-Finnish (FIN) AF: 0.267 AC: 14212 AN: 53314

Middle Eastern (MID) AF: 0.158 AC: 903 AN: 5718

European-Non Finnish (NFE) AF: 0.222 AC: 246509 AN: 1111308

Other (OTH) AF: 0.237 AC: 14311 AN: 60338

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

African (AFR) AF: 0.377 AC: 15645 AN: 41476

American (AMR) AF: 0.164 AC: 2500 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2129 AN: 5154

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4830

European-Finnish (FIN) AF: 0.278 AC: 2940 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15027 AN: 68016

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.227 Hom.: 11600

Bravo AF: 0.265

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.81
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs525735; hg19: chr5-38881628; COSMIC: COSV57094191;