Genetic Variant ENST00000512519.2:n.75C>A (chr5-38845758-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000512519.2(OSMR-DT):n.75C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,724 control chromosomes in the GnomAD database, including 398 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 0.023 ( 397 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1 hom. )

Consequence

OSMR-DT
ENST00000512519.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

5 publications found

Variant links:

Genes affected

OSMR-DT (HGNC:50296): (OSMR divergent transcript)

OSMR-DT links:

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

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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512519.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
OSMR-DT	NR_109951.1	n.72C>A	non_coding_transcript_exon	Exon 1 of 4
OSMR-DT	NR_171676.1	n.12C>A	non_coding_transcript_exon	Exon 1 of 3
OSMR-DT	NR_171677.1	n.12C>A	non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
OSMR-DT	ENST00000512519.2	TSL:2	n.75C>A	non_coding_transcript_exon	Exon 1 of 2
OSMR-DT	ENST00000513480.2	TSL:4	n.17C>A	non_coding_transcript_exon	Exon 1 of 4
OSMR-DT	ENST00000636516.3	TSL:5	n.61C>A	non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3493

AN:

152124

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.00762

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0287

GnomAD4 exome

AF:

0.0249

AC:

AN:

482

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

AN XY:

378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.286

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0125

AC:

AN:

400

Other (OTH)

AF:

0.115

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0229

AC:

3491

AN:

152242

Hom.:

397

Cov.:

AF XY:

0.0245

AC XY:

1820

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00447

AC:

186

AN:

41582

American (AMR)

AF:

0.0118

AC:

180

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.383

AC:

1957

AN:

5106

South Asian (SAS)

AF:

0.0215

AC:

104

AN:

4828

European-Finnish (FIN)

AF:

0.00762

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

876

AN:

68014

Other (OTH)

AF:

0.0312

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

132

263

395

526

658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0166

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.132

AC:

458

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.4

(source)

DANN

Benign

0.90

PhyloP100

0.099

PromoterAI

-0.17

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over