rs1969589

Positions:

• chr15-93044800-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020211.3(RGMA):​c.*198A>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 0.901 in 599,176 control chromosomes in the GnomAD database, including 250,776 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 0.92 (65316 hom., cov: 32)
  • Exomes 𝑓: 0.90 (185460 hom.)
• Consequence: RGMA NM_020211.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596

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]

RGMA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGMA	NM_020211.3	c.*198A>G		3_prime_UTR_variant	4/4	ENST00000329082.12	NP_064596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGMA	ENST00000329082	c.*198A>G		3_prime_UTR_variant	4/4	1	NM_020211.3	ENSP00000330005.7

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139542 AN: 152092 Hom.: 65272 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.913

GnomAD4 exome AF: 0.896 AC: 400322 AN: 446966 Hom.: 185460 Cov.: 4 AF XY: 0.892 AC XY: 209567 AN XY: 234902

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.960

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.814

Gnomad4 FIN exome AF: 0.938

Gnomad4 NFE exome AF: 0.972

Gnomad4 OTH exome AF: 0.911

GnomAD4 genome AF: 0.917 AC: 139632 AN: 152210 Hom.: 65316 Cov.: 32 AF XY: 0.906 AC XY: 67457 AN XY: 74426

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.961

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.936

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.906

Alfa AF: 0.923 Hom.: 9559

Bravo AF: 0.905

Asia WGS AF: 0.638 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs1969589; hg19: chr15-93588030; COSMIC: COSV61233816; COSMIC: COSV61233816;