NM_003999.3:c.991+5605G>A

Variant names:

• chr5-38891795-G-A
• rs3792860
• NM_003999.3:c.991+5605G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003999.3(OSMR):​c.991+5605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,168 control chromosomes in the GnomAD database, including 2,769 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 0.17 (2769 hom., cov: 32)
• Consequence: OSMR NM_003999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.236 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.991+5605G>A		intron	N/A	NP_003990.1
	OSMR	NM_001323506.2		c.991+5605G>A		intron	N/A	NP_001310435.1
	OSMR	NM_001323505.2		c.991+5605G>A		intron	N/A	NP_001310434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSMR	ENST00000274276.8	TSL:1 MANE Select	c.991+5605G>A		intron	N/A	ENSP00000274276.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26270 AN: 152050 Hom.: 2766 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.173 AC: 26272 AN: 152168 Hom.: 2769 Cov.: 32 AF XY: 0.175 AC XY: 12983 AN XY: 74384

African (AFR) AF: 0.0582 AC: 2418 AN: 41544

American (AMR) AF: 0.243 AC: 3714 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3468

East Asian (EAS) AF: 0.139 AC: 721 AN: 5170

South Asian (SAS) AF: 0.128 AC: 618 AN: 4830

European-Finnish (FIN) AF: 0.215 AC: 2277 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15019 AN: 67966

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.209 Hom.: 1850

Bravo AF: 0.170

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.79
DANN	Benign	0.35
PhyloP100		-0.92
Mutation Taster		=100/0	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: rs3792860; hg19: chr5-38891897;