Genetic Variant MAGEB6B:p.Leu282Leu (chrX-26161444-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001396029.1(MAGEB6B):c.844C>T(p.Leu282Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,083,370 control chromosomes in the GnomAD database, including 1 homozygotes. There are 184 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 0.00033 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00053 ( 1 hom. 173 hem. )

Consequence

MAGEB6B
NM_001396029.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.28

Variant links:

Genes affected

MAGEB6B (HGNC:28824): (MAGE family member B6B) Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAGEB6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant X-26161444-C-T is Benign according to our data. Variant chrX-26161444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660204.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB6B	NM_001396029.1 link	c.844C>T	p.Leu282Leu	synonymous_variant	Exon 1 of 1	ENST00000416929.3	NP_001382958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB6B	ENST00000416929.3 link	c.844C>T	p.Leu282Leu	synonymous_variant	Exon 1 of 1	6	NM_001396029.1	ENSP00000488257.1		A0A0J9YX57

Frequencies

GnomAD3 genomes

AF:

0.000333

AC:

AN:

111207

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

AN XY:

33377

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000956

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000463

AC:

AN:

183394

Hom.:

AF XY:

0.000531

AC XY:

AN XY:

67836

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00142

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000660

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000534

AC:

519

AN:

972163

Hom.:

Cov.:

AF XY:

0.000595

AC XY:

173

AN XY:

290975

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000570

Gnomad4 ASJ exome

AF:

0.0000537

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.000560

Gnomad4 OTH exome

AF:

0.000524

GnomAD4 genome

AF:

0.000333

AC:

AN:

111207

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

AN XY:

33377

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.000374

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEB6B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.66

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over