NM_003999.3:c.2044+219T>C

Variant names:

• chr5-38924814-T-C
• rs168568
• NM_003999.3:c.2044+219T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003999.3(OSMR):​c.2044+219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,880 control chromosomes in the GnomAD database, including 5,214 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 0.25 (5214 hom., cov: 31)
• Consequence: OSMR NM_003999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• Publications: 9 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 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.2044+219T>C		intron	N/A	NP_003990.1
	OSMR	NM_001323506.2		c.2047+219T>C		intron	N/A	NP_001310435.1
	OSMR	NM_001323505.2		c.2044+219T>C		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.2044+219T>C		intron	N/A	ENSP00000274276.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38127 AN: 151762 Hom.: 5220 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38132 AN: 151880 Hom.: 5214 Cov.: 31 AF XY: 0.253 AC XY: 18800 AN XY: 74254

African (AFR) AF: 0.357 AC: 14760 AN: 41372

American (AMR) AF: 0.161 AC: 2455 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1680 AN: 5168

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4808

European-Finnish (FIN) AF: 0.261 AC: 2750 AN: 10532

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13799 AN: 67952

Other (OTH) AF: 0.221 AC: 464 AN: 2102

Alfa AF: 0.214 Hom.: 2238

Bravo AF: 0.246

Asia WGS AF: 0.246 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs168568; hg19: chr5-38924916;