rs6614327

Positions:

• chrX-51827017-G-A

Variant summary

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

The NM_001005332.2(MAGED1):​c.-37+23900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 111,918 control chromosomes in the GnomAD database, including 105 homozygotes. There are 1,356 hemizygotes in GnomAD. 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 0.038 (105 hom., 1356 hem., cov: 24)
• Consequence: MAGED1 NM_001005332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

MAGED1 (HGNC:6813): (MAGE family member D1) This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGED1	NM_001005332.2	c.-37+23900G>A		intron_variant			NP_001005332.1
MAGED1	XM_011530835.3	c.-37+7609G>A		intron_variant			XP_011529137.1
MAGED1	XM_047442676.1	c.-30523+23900G>A		intron_variant			XP_047298632.1
MAGED1	XM_047442677.1	c.-111+23900G>A		intron_variant			XP_047298633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000375772.7	c.-37+23900G>A		intron_variant		5		ENSP00000364927	P2

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 4237 AN: 111864 Hom.: 107 Cov.: 24 AF XY: 0.0398 AC XY: 1355 AN XY: 34048

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0519

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

GnomAD4 genome AF: 0.0378 AC: 4230 AN: 111918 Hom.: 105 Cov.: 24 AF XY: 0.0398 AC XY: 1356 AN XY: 34112

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0903

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0513

Alfa AF: 0.0340 Hom.: 269

Bravo AF: 0.0439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.58

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: rs6614327; hg19: chrX-51570113;