chr5-38876259-G-A

Variant names:

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

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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 18	1	NM_003999.3	ENSP00000274276.3
OSMR	ENST00000502536.5	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 7	1		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

Gnomad4 AFR exome AF: 0.0827 AC: 2767 AN: 33456

Gnomad4 AMR exome AF: 0.00463 AC: 207 AN: 44704

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26124

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39668

Gnomad4 SAS exome AF: 0.000186 AC: 16 AN: 86202

Gnomad4 FIN exome AF: 0.0000562 AC: 3 AN: 53412

Gnomad4 NFE exome AF: 0.000212 AC: 236 AN: 1111754

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0762 AC: 0.0762208 AN: 0.0762208

Gnomad4 AMR AF: 0.00609 AC: 0.00608958 AN: 0.00608958

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000412 AC: 0.000411922 AN: 0.000411922

Gnomad4 OTH AF: 0.0133 AC: 0.0132953 AN: 0.0132953

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

OSMR-related disorder Benign:1

Apr 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.45
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

Publications

LitVar

Other links and lift over

dbSNP: rs16867807; hg19: chr5-38876361;