rs199978505

Variant names:

• chrX-30250613-C-G
• rs199978505
• NM_177404.3:c.120C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-30250613-C-G
• chrX-30250613-C-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.120C>G​(p.Ser40Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,207,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 0.000062 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000026 (0 hom. 10 hem.)
• Consequence: MAGEB1 NM_177404.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.114
• Publications: 2 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=-0.83).
• BP6: Variant X-30250613-C-G is Benign according to our data. Variant chrX-30250613-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 751136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.114 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3	c.120C>G	p.Ser40Ser	synonymous_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1
MAGEB1	NM_002363.5	c.120C>G	p.Ser40Ser	synonymous_variant	Exon 4 of 4		NP_002354.2
MAGEB1	NM_177415.3	c.120C>G	p.Ser40Ser	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.120C>G	p.Ser40Ser	synonymous_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2
MAGEB1	ENST00000378981.8	c.120C>G	p.Ser40Ser	synonymous_variant	Exon 4 of 4	1		ENSP00000368264.3
MAGEB1	ENST00000397550.6	c.120C>G	p.Ser40Ser	synonymous_variant	Exon 3 of 3	1		ENSP00000380683.1

Frequencies

GnomAD3 genomes AF: 0.0000621 AC: 7 AN: 112764 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000927

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000345 AC: 6 AN: 173816 AF XY: 0.0000169

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000372

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000653

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000265 AC: 29 AN: 1095000 Hom.: 0 Cov.: 31 AF XY: 0.0000277 AC XY: 10 AN XY: 360582

African (AFR) AF: 0.00 AC: 0 AN: 26308

American (AMR) AF: 0.00 AC: 0 AN: 35005

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19331

East Asian (EAS) AF: 0.00 AC: 0 AN: 30047

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53425

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40363

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.0000309 AC: 26 AN: 840432

Other (OTH) AF: 0.0000435 AC: 2 AN: 45960

GnomAD4 genome AF: 0.0000620 AC: 7 AN: 112817 Hom.: 0 Cov.: 24 AF XY: 0.0000572 AC XY: 2 AN XY: 34975

African (AFR) AF: 0.00 AC: 0 AN: 31115

American (AMR) AF: 0.0000926 AC: 1 AN: 10797

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53284

Other (OTH) AF: 0.00 AC: 0 AN: 1542

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.46
PhyloP100		-0.11
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: rs199978505; hg19: chrX-30268730; COSMIC: COSV66775587;