rs2545680

Variant names:

• chr5-98796179-A-G
• rs2545680
• NM_001366508.1:c.*2426A>G

Variant summary

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

The NM_001366508.1(RGMB):​c.*2426A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,220 control chromosomes in the GnomAD database, including 1,141 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 0.11 (1141 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGMB NM_001366508.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 11 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]

ENSG00000279232 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGMB	NM_001366508.1	c.*2426A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000513185.3	NP_001353437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGMB	ENST00000513185.3	c.*2426A>G		3_prime_UTR_variant	Exon 3 of 3	2	NM_001366508.1	ENSP00000423256.1
RGMB	ENST00000308234.11	c.*2426A>G		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000308219.7
RGMB	ENST00000508978.1	n.245-2282A>G		intron_variant	Intron 1 of 1	3
ENSG00000279232	ENST00000729266.1	n.413-1055T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16960 AN: 152102 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.141

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.111 AC: 16963 AN: 152220 Hom.: 1141 Cov.: 32 AF XY: 0.108 AC XY: 8042 AN XY: 74430

African (AFR) AF: 0.0727 AC: 3019 AN: 41512

American (AMR) AF: 0.101 AC: 1552 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3470

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5180

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4824

European-Finnish (FIN) AF: 0.0728 AC: 773 AN: 10614

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9842 AN: 68006

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.141 Hom.: 2636

Bravo AF: 0.114

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		0.099
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: rs2545680; hg19: chr5-98131883;