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GeneBe

15-93045427-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020211.3(RGMA):c.924C>T(p.Asp308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,156 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00069 ( 7 hom. )

Consequence

RGMA
NM_020211.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.51
Variant links:
Genes affected
RGMA (HGNC:30308): (repulsive guidance molecule BMP co-receptor a) This gene encodes a member of the repulsive guidance molecule family. The encoded protein is a glycosylphosphatidylinositol-anchored glycoprotein that functions as an axon guidance protein in the developing and adult central nervous system. This protein may also function as a tumor suppressor in some cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-93045427-G-A is Benign according to our data. Variant chr15-93045427-G-A is described in ClinVar as [Benign]. Clinvar id is 712174.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.51 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00672 (1023/152270) while in subpopulation AFR AF= 0.0235 (977/41552). AF 95% confidence interval is 0.0223. There are 13 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGMANM_020211.3 linkuse as main transcriptc.924C>T p.Asp308= synonymous_variant 4/4 ENST00000329082.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGMAENST00000329082.12 linkuse as main transcriptc.924C>T p.Asp308= synonymous_variant 4/41 NM_020211.3 P2Q96B86-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00670
AC:
1019
AN:
152152
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0235
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00167
AC:
411
AN:
246818
Hom.:
2
AF XY:
0.00122
AC XY:
164
AN XY:
134344
show subpopulations
Gnomad AFR exome
AF:
0.0237
Gnomad AMR exome
AF:
0.00107
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000450
Gnomad OTH exome
AF:
0.000332
GnomAD4 exome
AF:
0.000690
AC:
1008
AN:
1460886
Hom.:
7
Cov.:
35
AF XY:
0.000588
AC XY:
427
AN XY:
726726
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00672
AC:
1023
AN:
152270
Hom.:
13
Cov.:
32
AF XY:
0.00629
AC XY:
468
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0235
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00346
Hom.:
2
Bravo
AF:
0.00774
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
9.5
Dann
Benign
0.56

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.

Other links and lift over

dbSNP: rs61733836; hg19: chr15-93588657; API