5-38857264-T-G

Variant names:

• chr5-38857264-T-G
• rs420444
• NM_003999.3:c.-14+10877T>G

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+10877T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,154 control chromosomes in the GnomAD database, including 2,919 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 0.19 (2919 hom., cov: 32)
• Consequence: OSMR NM_003999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3	c.-14+10877T>G		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+10877T>G		intron_variant	Intron 1 of 17	1	NM_003999.3	ENSP00000274276.3
OSMR	ENST00000502536.5	c.-14+11138T>G		intron_variant	Intron 1 of 6	1		ENSP00000422023.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29160 AN: 152036 Hom.: 2917 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.192 AC: 29178 AN: 152154 Hom.: 2919 Cov.: 32 AF XY: 0.193 AC XY: 14327 AN XY: 74368

African (AFR) AF: 0.226 AC: 9398 AN: 41504

American (AMR) AF: 0.197 AC: 3012 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3466

East Asian (EAS) AF: 0.0545 AC: 283 AN: 5190

South Asian (SAS) AF: 0.151 AC: 730 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2458 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12169 AN: 68000

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.175 Hom.: 4041

Bravo AF: 0.190

Asia WGS AF: 0.0930 AC: 323 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs420444; hg19: chr5-38857366;