rs16867807

Variant names:

• chr5-38876259-G-A
• rs16867807
• NM_003999.3:c.132G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-38876259-G-A
• chr5-38876259-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003999.3(OSMR):​c.132G>A​(p.Thr44Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,418 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (132 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (140 hom.)
• Consequence: OSMR NM_003999.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.250
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-38876259-G-A is Benign according to our data. Variant chr5-38876259-G-A is described in ClinVar as Benign. ClinVar VariationId is 776041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 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.132G>A	p.Thr44Thr	synonymous	Exon 3 of 18	NP_003990.1
	OSMR	NM_001323506.2		c.132G>A	p.Thr44Thr	synonymous	Exon 3 of 18	NP_001310435.1
	OSMR	NM_001323505.2		c.132G>A	p.Thr44Thr	synonymous	Exon 3 of 18	NP_001310434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	ENST00000274276.8	TSL:1 MANE Select	c.132G>A	p.Thr44Thr	synonymous	Exon 3 of 18	ENSP00000274276.3
	OSMR	ENST00000502536.5	TSL:1	c.132G>A	p.Thr44Thr	synonymous	Exon 3 of 7	ENSP00000422023.1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3298 AN: 151840 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00600 AC: 1508 AN: 251128 AF XY: 0.00458

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00243 AC: 3556 AN: 1461460 Hom.: 140 Cov.: 30 AF XY: 0.00208 AC XY: 1512 AN XY: 727018

African (AFR) AF: 0.0827 AC: 2767 AN: 33456

American (AMR) AF: 0.00463 AC: 207 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86202

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53412

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.000212 AC: 236 AN: 1111754

Other (OTH) AF: 0.00515 AC: 311 AN: 60374

GnomAD4 genome AF: 0.0218 AC: 3306 AN: 151958 Hom.: 132 Cov.: 33 AF XY: 0.0205 AC XY: 1526 AN XY: 74282

African (AFR) AF: 0.0762 AC: 3156 AN: 41406

American (AMR) AF: 0.00609 AC: 93 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67974

Other (OTH) AF: 0.0133 AC: 28 AN: 2106

Alfa AF: 0.00833 Hom.: 62

Bravo AF: 0.0256

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	OSMR-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.45
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs16867807; hg19: chr5-38876361;