rs1534780

chr15-93081984-C-Gchr15-93081984-C-T

Variant summary

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

The NM_020211.3(RGMA):c.14+6935G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,152 control chromosomes in the GnomAD database, including 11,539 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 0.38 (11539 hom., cov: 34)
• Consequence: RGMA NM_020211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGMA	NM_020211.3	c.14+6935G>C		intron_variant		ENST00000329082.12
RGMA	NM_001166287.2	c.-35+6297G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGMA	ENST00000329082.12	c.14+6935G>C		intron_variant		1	NM_020211.3	P2
RGMA	ENST00000543599.5	c.-35+6297G>C		intron_variant		5		A2
RGMA	ENST00000555598.1	c.-35+6297G>C		intron_variant		4
RGMA	ENST00000556950.1	c.-35+6415G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58273 AN: 152034 Hom.: 11538 Cov.: 34

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.383 AC: 58282 AN: 152152 Hom.: 11539 Cov.: 34 AF XY: 0.382 AC XY: 28446 AN XY: 74384

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.386

Alfa AF: 0.406 Hom.: 1556

Bravo AF: 0.381

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.2
Dann	Benign	0.66

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: rs1534780; hg19: chr15-93625213;