rs720309

Variant names:

• chr19-35307013-T-A
• rs720309
• NM_002361.4:c.1232-2861T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002361.4(MAG):​c.1232-2861T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,304 control chromosomes in the GnomAD database, including 1,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1430 hom., cov: 33)
• Consequence: MAG NM_002361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 75

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4	c.1232-2861T>A		intron_variant	Intron 7 of 10	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.1157-2861T>A		intron_variant	Intron 7 of 10		NP_001186145.1
MAG	NM_080600.3	c.1232-2861T>A		intron_variant	Intron 7 of 11		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.1232-2861T>A		intron_variant	Intron 7 of 10	1	NM_002361.4	ENSP00000376048.2
MAG	ENST00000537831.2	c.1157-2861T>A		intron_variant	Intron 7 of 10	1		ENSP00000440695.1
MAG	ENST00000361922.8	c.1232-2861T>A		intron_variant	Intron 7 of 11	1		ENSP00000355234.4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20129 AN: 152186 Hom.: 1426 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20153 AN: 152304 Hom.: 1430 Cov.: 33 AF XY: 0.134 AC XY: 9962 AN XY: 74478

African (AFR) AF: 0.102 AC: 4248 AN: 41564

American (AMR) AF: 0.182 AC: 2787 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.158 AC: 818 AN: 5176

South Asian (SAS) AF: 0.188 AC: 908 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10620

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9143 AN: 68026

Other (OTH) AF: 0.136 AC: 287 AN: 2116

Alfa AF: 0.131 Hom.: 186

Bravo AF: 0.135

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs720309; hg19: chr19-35797916;