5-98774042-C-T

Variant names:

• chr5-98774042-C-T
• rs969052170
• NM_001366508.1:c.-29C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001366508.1(RGMB):​c.-29C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 780,178 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: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: RGMB NM_001366508.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.898
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.212109).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.-29C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001366508.1	MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.95C>T	p.Pro32Leu	missense	Exon 3 of 5	NP_001012779.2	J3KNF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	ENST00000513185.3	TSL:2 MANE Select	c.-29C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.95C>T	p.Pro32Leu	missense	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000513185.3	TSL:2 MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 3	ENSP00000423256.1	Q6NW40

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151966 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000140 AC: 1 AN: 71212 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000887

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: 0.00000637 AC: 4 AN: 628212 Hom.: 0 Cov.: 8 AF XY: 0.00000300 AC XY: 1 AN XY: 333594

African (AFR) AF: 0.000154 AC: 2 AN: 13000

American (AMR) AF: 0.0000471 AC: 1 AN: 21222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18422

East Asian (EAS) AF: 0.00 AC: 0 AN: 24856

South Asian (SAS) AF: 0.00 AC: 0 AN: 56926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2702

European-Non Finnish (NFE) AF: 0.00000238 AC: 1 AN: 419524

Other (OTH) AF: 0.00 AC: 0 AN: 31602

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151966 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74224

African (AFR) AF: 0.0000725 AC: 3 AN: 41406

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.12
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.48	T
PhyloP100		0.90
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.25
Sift	Benign	0.094	T
Sift4G	Benign	0.16	T
Vest4		0.19
MutPred		0.13		Loss of glycosylation at P32 (P = 0.0061)
MVP		0.73
MPC		0.32
ClinPred		0.98	D
GERP RS		1.3
PromoterAI		-0.029	Neutral
gMVP		0.31
Mutation Taster		=81/19	polymorphism

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: rs969052170; hg19: chr5-98109746;