NM_003999.3:c.-14+4400G>A

Variant names:

• chr5-38850787-G-A
• rs3805558
• NM_003999.3:c.-14+4400G>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.-14+4400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,090 control chromosomes in the GnomAD database, including 4,891 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 0.25 (4891 hom., cov: 32)
• Consequence: OSMR NM_003999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3	c.-14+4400G>A		intron_variant	Intron 1 of 17	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.-14+4400G>A		intron_variant	Intron 1 of 17	1	NM_003999.3	ENSP00000274276.3
OSMR	ENST00000502536.5	c.-14+4661G>A		intron_variant	Intron 1 of 6	1		ENSP00000422023.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37635 AN: 151972 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.247 AC: 37627 AN: 152090 Hom.: 4891 Cov.: 32 AF XY: 0.247 AC XY: 18350 AN XY: 74346

African (AFR) AF: 0.194 AC: 8039 AN: 41470

American (AMR) AF: 0.273 AC: 4174 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.172 AC: 891 AN: 5180

South Asian (SAS) AF: 0.398 AC: 1917 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18372 AN: 67996

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.270 Hom.: 3460

Bravo AF: 0.247

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.56
PhyloP100		-1.7
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: rs3805558; hg19: chr5-38850889;