chr5-38925268-C-T

Variant names:

• chr5-38925268-C-T
• rs2289925
• NM_003999.3:c.2109C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_003999.3(OSMR):​c.2109C>T​(p.Asn703Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,822 control chromosomes in the GnomAD database, including 58 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 0.0016 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (51 hom.)
• Consequence: OSMR NM_003999.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• 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: AD, SD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial primary localized cutaneous amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00158 (241/152120) while in subpopulation EAS AF = 0.0363 (188/5174). AF 95% confidence interval is 0.0321. There are 7 homozygotes in GnomAd4. There are 145 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 241 AD,SD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	NM_003999.3	MANE Select	c.2109C>T	p.Asn703Asn	synonymous	Exon 15 of 18	NP_003990.1	Q99650-1
	OSMR	NM_001323506.2		c.2112C>T	p.Asn704Asn	synonymous	Exon 15 of 18	NP_001310435.1
	OSMR	NM_001323505.2		c.2109C>T	p.Asn703Asn	synonymous	Exon 15 of 18	NP_001310434.1	Q99650-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	ENST00000274276.8	TSL:1 MANE Select	c.2109C>T	p.Asn703Asn	synonymous	Exon 15 of 18	ENSP00000274276.3	Q99650-1
	OSMR	ENST00000880314.1		c.2112C>T	p.Asn704Asn	synonymous	Exon 15 of 18	ENSP00000550373.1
	OSMR	ENST00000880315.1		c.2112C>T	p.Asn704Asn	synonymous	Exon 15 of 18	ENSP00000550374.1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 241 AN: 152004 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00295 AC: 741 AN: 251400 AF XY: 0.00276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0349

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00148 AC: 2168 AN: 1461702 Hom.: 51 Cov.: 32 AF XY: 0.00152 AC XY: 1108 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0437 AC: 1733 AN: 39694

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86254

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000152 AC: 169 AN: 1111844

Other (OTH) AF: 0.00162 AC: 98 AN: 60388

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152120 Hom.: 7 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41504

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5174

South Asian (SAS) AF: 0.00478 AC: 23 AN: 4812

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67996

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000463 Hom.: 1

Bravo AF: 0.00187

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.88
DANN	Benign	0.33
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

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: rs2289925; hg19: chr5-38925370;