dbSNP rs1239345: OSMR:n.72+4471T>C (chr5-38937006-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000508882.1(OSMR):n.72+4471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 152,312 control chromosomes in the GnomAD database, including 138 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 0.033 ( 138 hom., cov: 33)

Consequence

OSMR
ENST00000508882.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

Publications

2 publications found

Variant links:

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

OSMR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
OSMR	XM_011514161.3 link	c.2370+4471T>C	intron_variant	Intron 17 of 17	XP_011512463.1
OSMR	XM_017010019.2 link	c.2367+4471T>C	intron_variant	Intron 17 of 17	XP_016865508.1
OSMR	XM_047417872.1 link	c.2367+4471T>C	intron_variant	Intron 17 of 17	XP_047273828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000508882.1 link	n.72+4471T>C		intron_variant	Intron 1 of 2	3		ENSP00000422372.1		H0Y8W9
OSMR	ENST00000509237.5 link	n.153+4471T>C		intron_variant	Intron 2 of 3	5		ENSP00000426729.1		H0YAD1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5043

AN:

152194

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00827

Gnomad SAS

AF:

0.0805

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0258

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

GnomAD4 genome

AF:

0.0331

AC:

5048

AN:

152312

Hom.:

138

Cov.:

AF XY:

0.0331

AC XY:

2465

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0640

AC:

2658

AN:

41562

American (AMR)

AF:

0.0278

AC:

425

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.00868

AC:

AN:

5186

South Asian (SAS)

AF:

0.0814

AC:

393

AN:

4828

European-Finnish (FIN)

AF:

0.00810

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0193

AC:

1313

AN:

68020

Other (OTH)

AF:

0.0260

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

239

478

717

956

1195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0336

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.32

PhyloP100

-0.31

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over