rs969052170

Variant names:

• chr5-98774042-C-A
• rs969052170
• ENST00000308234.11:c.95C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-98774042-C-A
• chr5-98774042-C-G
• chr5-98774042-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001012761.3(RGMB):​c.95C>A​(p.Pro32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000796 in 628,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: RGMB NM_001012761.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23337218).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012761.3. 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>A		5_prime_UTR	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.95C>A	p.Pro32Gln	missense	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.95C>A	p.Pro32Gln	missense	Exon 3 of 5	NP_001353438.1	J3KNF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	ENST00000308234.11	TSL:1	c.95C>A	p.Pro32Gln	missense	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000513185.3	TSL:2 MANE Select	c.-29C>A		5_prime_UTR	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000894564.1		c.-29C>A		5_prime_UTR	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000140 AC: 1 AN: 71212 AF XY: 0.0000240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000514

GnomAD4 exome AF: 0.00000796 AC: 5 AN: 628212 Hom.: 0 Cov.: 8 AF XY: 0.00000600 AC XY: 2 AN XY: 333594

African (AFR) AF: 0.00 AC: 0 AN: 13000

American (AMR) AF: 0.00 AC: 0 AN: 21222

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

East Asian (EAS) AF: 0.000161 AC: 4 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: 0.00 AC: 0 AN: 419524

Other (OTH) AF: 0.0000316 AC: 1 AN: 31602

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Benign	0.96
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.077	T
PhyloP100		0.90
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.20
Sift	Benign	0.27	T
Sift4G	Benign	0.39	T
Vest4		0.22
MutPred		0.13		Loss of glycosylation at P32 (P = 0.0061)
MVP		0.78
MPC		0.23
ClinPred		0.87	D
GERP RS		1.3
PromoterAI		-0.072	Neutral
gMVP		0.38
Mutation Taster		=79/21	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;