rs1389589451

Variant names:

• chr5-98774122-G-A
• rs1389589451
• NM_001366508.1:c.52G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-98774122-G-A
• chr5-98774122-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366508.1(RGMB):​c.52G>A​(p.Glu18Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000313 in 1,276,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: RGMB NM_001366508.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47
• Publications: 0 publications found

Genes affected

RGMB (HGNC:26896): (repulsive guidance molecule BMP co-receptor b) RGMB is a glycosylphosphatidylinositol (GPI)-anchored member of the repulsive guidance molecule family (see RGMA, MIM 607362) and contributes to the patterning of the developing nervous system (Samad et al., 2005 [PubMed 15671031]).[supplied by OMIM, Apr 2009]

RGMB-AS1 (HGNC:48666): (RGMB antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31932253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	NM_001366508.1	MANE Select	c.52G>A	p.Glu18Lys	missense	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.175G>A	p.Glu59Lys	missense	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.175G>A	p.Glu59Lys	missense	Exon 3 of 5	NP_001353438.1	J3KNF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	ENST00000513185.3	TSL:2 MANE Select	c.52G>A	p.Glu18Lys	missense	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.175G>A	p.Glu59Lys	missense	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000894564.1		c.52G>A	p.Glu18Lys	missense	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000306 AC: 3 AN: 98174 AF XY: 0.0000363

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000313 AC: 4 AN: 1276152 Hom.: 0 Cov.: 19 AF XY: 0.00000316 AC XY: 2 AN XY: 633238

African (AFR) AF: 0.00 AC: 0 AN: 26096

American (AMR) AF: 0.0000918 AC: 3 AN: 32680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23492

East Asian (EAS) AF: 0.00 AC: 0 AN: 31094

South Asian (SAS) AF: 0.00 AC: 0 AN: 74628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 995324

Other (OTH) AF: 0.00 AC: 0 AN: 53920

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.58	N
REVEL	Uncertain	0.30
Sift	Benign	0.17	T
Sift4G	Benign	0.069	T
Polyphen		0.0010	B
Vest4		0.29
MutPred		0.39		Gain of ubiquitination at E18 (P = 0.0104)
MVP		0.66
MPC		0.90
ClinPred		0.28	T
GERP RS		4.0
PromoterAI		-0.0078	Neutral
Varity_R		0.21
gMVP		0.54
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1389589451; hg19: chr5-98109826;