rs4777760

Positions:

• chr15-93059088-G-A
• chr15-93059088-G-C

Variant summary

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

The NM_020211.3(RGMA):​c.131-6581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,936 control chromosomes in the GnomAD database, including 19,699 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 0.50 (19699 hom., cov: 32)
• Consequence: RGMA NM_020211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGMA	NM_020211.3	c.131-6581C>T		intron_variant		ENST00000329082.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGMA	ENST00000329082.12	c.131-6581C>T		intron_variant		1	NM_020211.3	P2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76462 AN: 151816 Hom.: 19677 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.504 AC: 76537 AN: 151936 Hom.: 19699 Cov.: 32 AF XY: 0.514 AC XY: 38199 AN XY: 74256

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.485

Alfa AF: 0.474 Hom.: 28709

Bravo AF: 0.493

Asia WGS AF: 0.735 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.70

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: rs4777760; hg19: chr15-93602317;