rs6614327

Variant names:

• chrX-51827017-G-A
• rs6614327
• NM_001005332.2:c.-37+23900G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAGED1	NM_001005332.2	c.-37+23900G>A		intron_variant	Intron 1 of 12		NP_001005332.1
MAGED1	XM_011530835.3	c.-37+7609G>A		intron_variant	Intron 2 of 13		XP_011529137.1
MAGED1	XM_047442676.1	c.-30523+23900G>A		intron_variant	Intron 1 of 14		XP_047298632.1
MAGED1	XM_047442677.1	c.-111+23900G>A		intron_variant	Intron 1 of 13		XP_047298633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000375772.7	c.-37+23900G>A		intron_variant	Intron 1 of 12	5		ENSP00000364927.3

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 4237 AN: 111864 Hom.: 107 Cov.: 24

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

African (AFR) AF: 0.0163 AC: 504 AN: 30853

American (AMR) AF: 0.0903 AC: 951 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 159 AN: 2640

East Asian (EAS) AF: 0.152 AC: 539 AN: 3537

South Asian (SAS) AF: 0.0918 AC: 245 AN: 2669

European-Finnish (FIN) AF: 0.0399 AC: 242 AN: 6066

Middle Eastern (MID) AF: 0.0184 AC: 4 AN: 217

European-Non Finnish (NFE) AF: 0.0284 AC: 1508 AN: 53192

Other (OTH) AF: 0.0513 AC: 78 AN: 1521

Alfa AF: 0.0338 Hom.: 800

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6614327; hg19: chrX-51570113;