5-98774158-C-T

Variant names:

• chr5-98774158-C-T
• rs1323266258
• NM_001366508.1:c.88C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001366508.1(RGMB):​c.88C>T​(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,347,410 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RGMB NM_001366508.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.

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.88C>T	p.Leu30Leu	synonymous	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.211C>T	p.Leu71Leu	synonymous	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.211C>T	p.Leu71Leu	synonymous	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.88C>T	p.Leu30Leu	synonymous	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.211C>T	p.Leu71Leu	synonymous	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000894564.1		c.88C>T	p.Leu30Leu	synonymous	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1347410 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 664532

African (AFR) AF: 0.0000729 AC: 2 AN: 27440

American (AMR) AF: 0.00 AC: 0 AN: 32130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23782

East Asian (EAS) AF: 0.00 AC: 0 AN: 31296

South Asian (SAS) AF: 0.00 AC: 0 AN: 75598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4056

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063236

Other (OTH) AF: 0.00 AC: 0 AN: 56266

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		1.4
PromoterAI		0.042	Neutral

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: rs1323266258; hg19: chr5-98109862;