5-38904380-G-A

Position:

• chr5-38904380-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000274276.8(OSMR):​c.1162G>A​(p.Glu388Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,992 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (30 hom.)
• Consequence: OSMR ENST00000274276.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.636

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004057616).
• BP6: Variant 5-38904380-G-A is Benign according to our data. Variant chr5-38904380-G-A is described in ClinVar as [Benign]. Clinvar id is 776042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1605/152232) while in subpopulation AFR AF= 0.0361 (1501/41522). AF 95% confidence interval is 0.0346. There are 23 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSMR	NM_003999.3	c.1162G>A	p.Glu388Lys	missense_variant	9/18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.1162G>A	p.Glu388Lys	missense_variant	9/18	1	NM_003999.3	ENSP00000274276	P1
OSMR	ENST00000513831.1			upstream_gene_variant		3		ENSP00000423913

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1604 AN: 152114 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00268 AC: 673 AN: 251254 Hom.: 9 AF XY: 0.00215 AC XY: 292 AN XY: 135784

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00118 AC: 1730 AN: 1461760 Hom.: 30 Cov.: 34 AF XY: 0.00107 AC XY: 780 AN XY: 727160

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.00306

GnomAD4 genome AF: 0.0105 AC: 1605 AN: 152232 Hom.: 23 Cov.: 32 AF XY: 0.00987 AC XY: 735 AN XY: 74434

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00194 Hom.: 5

Bravo AF: 0.0120

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0311 AC: 137

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00321 AC: 390

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.1
DANN	Benign	0.86
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.65	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.021
Sift	Benign	0.39	T
Sift4G	Uncertain	0.056	T
Polyphen		0.067	B
Vest4		0.16
MVP		0.37
MPC		0.099
ClinPred		0.00061	T
GERP RS		-0.87
Varity_R		0.037
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35727755; hg19: chr5-38904482;