X-30242934-C-A

Position:

• chrX-30242934-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002367.4(MAGEB4):​c.799C>A​(p.Arg267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,210,535 control chromosomes in the GnomAD database, including 59 homozygotes. There are 887 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (34 hom., 453 hem., cov: 24)
  • Exomes 𝑓: 0.0015 (25 hom. 434 hem.)
• Consequence: MAGEB4 NM_002367.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

Genes affected

MAGEB4 (HGNC:6811): (MAGE family member B4) 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. The MAGEB genes are clustered on chromosome Xp22-p21. This gene sequence ends in the first intron of MAGEB1, another family member. This gene is expressed in testis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050359666).
• BP6: Variant X-30242934-C-A is Benign according to our data. Variant chrX-30242934-C-A is described in ClinVar as [Benign]. Clinvar id is 713256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (1655/112496) while in subpopulation AFR AF= 0.0507 (1572/31002). AF 95% confidence interval is 0.0486. There are 34 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB4	NM_002367.4	c.799C>A	p.Arg267Ser	missense_variant	1/1	ENST00000378982.4	NP_002358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB4	ENST00000378982.4	c.799C>A	p.Arg267Ser	missense_variant	1/1	6	NM_002367.4	ENSP00000368266.2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1655 AN: 112442 Hom.: 34 Cov.: 24 AF XY: 0.0131 AC XY: 454 AN XY: 34584

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000131

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00399 AC: 732 AN: 183441 Hom.: 8 AF XY: 0.00270 AC XY: 183 AN XY: 67885

Gnomad AFR exome AF: 0.0484

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000157

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.00146 AC: 1598 AN: 1098039 Hom.: 25 Cov.: 58 AF XY: 0.00119 AC XY: 434 AN XY: 363397

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000923

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000689

Gnomad4 OTH exome AF: 0.00351

GnomAD4 genome AF: 0.0147 AC: 1655 AN: 112496 Hom.: 34 Cov.: 24 AF XY: 0.0131 AC XY: 453 AN XY: 34648

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000131

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.000548 Hom.: 7

Bravo AF: 0.0168

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0472 AC: 181

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00464 AC: 564

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.92	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.96
DANN	Benign	0.65
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.022
Sift	Benign	0.20	T
Sift4G	Benign	0.55	T
Polyphen		0.43	B
Vest4		0.044
MVP		0.081
MPC		0.26
ClinPred		0.0062	T
GERP RS		-4.5
Varity_R		0.18
gMVP		0.53

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: rs112995221; hg19: chrX-30261051;