Variant rs3746248 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002361.4(MAG):c.462G>A(p.Glu154Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,605,214 control chromosomes in the GnomAD database, including 53,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 12254 hom., cov: 26)

Exomes 𝑓: 0.22 ( 41702 hom. )

Consequence

MAG
NM_002361.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0520

Variant links:

Genes affected

MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

MAG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-35299600-G-A is Benign according to our data. Variant chr19-35299600-G-A is described in ClinVar as [Benign]. Clinvar id is 1168416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAG	NM_002361.4 linkuse as main transcript	c.462G>A	p.Glu154Glu	synonymous_variant	5/11	ENST00000392213.8	NP_002352.1	P20916-1Q53ES7
MAG	NM_001199216.2 linkuse as main transcript	c.387G>A	p.Glu129Glu	synonymous_variant	5/11		NP_001186145.1	P20916-3
MAG	NM_080600.3 linkuse as main transcript	c.462G>A	p.Glu154Glu	synonymous_variant	5/12		NP_542167.1	P20916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8 linkuse as main transcript	c.462G>A	p.Glu154Glu	synonymous_variant	5/11	1	NM_002361.4	ENSP00000376048.2		P20916-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52391

AN:

151296

Hom.:

12231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.258

AC:

62980

AN:

244250

Hom.:

9863

AF XY:

0.250

AC XY:

33194

AN XY:

132608

show subpopulations

Gnomad AFR exome

AF:

0.680

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.361

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.225

AC:

326661

AN:

1453800

Hom.:

41702

Cov.:

AF XY:

0.224

AC XY:

161564

AN XY:

721642

show subpopulations

Gnomad4 AFR exome

AF:

0.686

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.347

AC:

52467

AN:

151414

Hom.:

12254

Cov.:

AF XY:

0.344

AC XY:

25421

AN XY:

73954

show subpopulations

Gnomad4 AFR

AF:

0.674

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.236

Hom.:

8899

Bravo

AF:

0.366

Asia WGS

AF:

0.358

AC:

1246

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 75

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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