chrX-30250580-C-T

Variant names:

• chrX-30250580-C-T
• rs369750525
• NM_177404.3:c.87C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_177404.3(MAGEB1):​c.87C>T​(p.His29His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000746 in 1,207,102 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.000070 (0 hom. 24 hem.)
• Consequence: MAGEB1 NM_177404.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.258
• Publications: 1 publications found

Genes affected

MAGEB1 (HGNC:6808): (MAGE family member B1) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region, and expressed in testis and in a significant fraction of tumors of various histological types. This gene and other MAGEB members are clustered on chromosome Xp22-p21. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene, however, the full length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-30250580-C-T is Benign according to our data. Variant chrX-30250580-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3	c.87C>T	p.His29His	synonymous_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1
MAGEB1	NM_002363.5	c.87C>T	p.His29His	synonymous_variant	Exon 4 of 4		NP_002354.2
MAGEB1	NM_177415.3	c.87C>T	p.His29His	synonymous_variant	Exon 3 of 3		NP_803134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB1	ENST00000397548.4	c.87C>T	p.His29His	synonymous_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2
MAGEB1	ENST00000378981.8	c.87C>T	p.His29His	synonymous_variant	Exon 4 of 4	1		ENSP00000368264.3
MAGEB1	ENST00000397550.6	c.87C>T	p.His29His	synonymous_variant	Exon 3 of 3	1		ENSP00000380683.1

Frequencies

GnomAD3 genomes AF: 0.000115 AC: 13 AN: 112781 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000561

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000873 AC: 15 AN: 171805 AF XY: 0.000104

Gnomad AFR exome AF: 0.0000810

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000765

Gnomad FIN exome AF: 0.000261

Gnomad NFE exome AF: 0.0000929

Gnomad OTH exome AF: 0.000463

GnomAD4 exome AF: 0.0000704 AC: 77 AN: 1094267 Hom.: 0 Cov.: 31 AF XY: 0.0000667 AC XY: 24 AN XY: 359963

African (AFR) AF: 0.0000760 AC: 2 AN: 26300

American (AMR) AF: 0.00 AC: 0 AN: 34869

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19312

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30043

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53308

European-Finnish (FIN) AF: 0.000124 AC: 5 AN: 40316

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4124

European-Non Finnish (NFE) AF: 0.0000714 AC: 60 AN: 840035

Other (OTH) AF: 0.000131 AC: 6 AN: 45960

GnomAD4 genome AF: 0.000115 AC: 13 AN: 112835 Hom.: 0 Cov.: 24 AF XY: 0.000114 AC XY: 4 AN XY: 34999

African (AFR) AF: 0.0000321 AC: 1 AN: 31138

American (AMR) AF: 0.00 AC: 0 AN: 10787

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.000562 AC: 2 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2713

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6236

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53299

Other (OTH) AF: 0.00 AC: 0 AN: 1544

Alfa AF: 0.000174 Hom.: 1

Bravo AF: 0.0000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.41
DANN	Benign	0.63
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

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: rs369750525; hg19: chrX-30268697; COSMIC: COSV66775520;