Variant 5-98779663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001366508.1(RGMB):c.220G>A(p.Val74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000959 in 1,574,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

RGMB
NM_001366508.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.184

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007478416).

BP6

Variant 5-98779663-G-A is Benign according to our data. Variant chr5-98779663-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2600810.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGMB	NM_001366508.1 linkuse as main transcript	c.220G>A	p.Val74Ile	missense_variant	2/3	ENST00000513185.3	NP_001353437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RGMB	ENST00000513185.3 linkuse as main transcript	c.220G>A	p.Val74Ile	missense_variant	2/3	2	NM_001366508.1	ENSP00000423256
RGMB	ENST00000308234.11 linkuse as main transcript	c.343G>A	p.Val115Ile	missense_variant	4/5	1		ENSP00000308219	P1
RGMB	ENST00000434027.2 linkuse as main transcript	n.991G>A		non_coding_transcript_exon_variant	4/4	2
RGMB	ENST00000504776.5 linkuse as main transcript	n.624G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000955

GnomAD3 exomes

AF:

0.000139

AC:

AN:

223294

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

119594

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.0000942

Gnomad ASJ exome

AF:

0.000136

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000842

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1422300

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

701814

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.0000717

Gnomad4 ASJ exome

AF:

0.0000426

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000882

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.00000367

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.000558

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000552

Hom.:

Bravo

AF:

0.000612

ESP6500AA

AF:

0.00222

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000182

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.17

DANN

Benign

0.90

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.16

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0075

T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.19

Sift

Benign

0.23

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.011

.;B

Vest4

0.093

MVP

0.70

MPC

0.19

ClinPred

0.0049

GERP RS

-5.0

Varity_R

0.19

gMVP

0.16

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over