rs7249617

Variant names:

• chr19-35305081-C-G
• rs7249617
• NM_002361.4:c.1231+2373C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-35305081-C-G
• chr19-35305081-C-T

Variant summary

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

The NM_002361.4(MAG):​c.1231+2373C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 152,196 control chromosomes in the GnomAD database, including 431 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 0.044 (431 hom., cov: 32)
• Consequence: MAG NM_002361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4	c.1231+2373C>G		intron_variant	Intron 7 of 10	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.1156+2373C>G		intron_variant	Intron 7 of 10		NP_001186145.1
MAG	NM_080600.3	c.1231+2373C>G		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.1231+2373C>G		intron_variant	Intron 7 of 10	1	NM_002361.4	ENSP00000376048.2
MAG	ENST00000537831.2	c.1156+2373C>G		intron_variant	Intron 7 of 10	1		ENSP00000440695.1
MAG	ENST00000361922.8	c.1231+2373C>G		intron_variant	Intron 7 of 11	1		ENSP00000355234.4

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6654 AN: 152078 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0438 AC: 6666 AN: 152196 Hom.: 431 Cov.: 32 AF XY: 0.0425 AC XY: 3164 AN XY: 74408

African (AFR) AF: 0.138 AC: 5707 AN: 41498

American (AMR) AF: 0.0139 AC: 212 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.0649 AC: 335 AN: 5164

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4826

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68014

Other (OTH) AF: 0.0313 AC: 66 AN: 2110

Alfa AF: 0.000777 Hom.: 1

Bravo AF: 0.0488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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: rs7249617; hg19: chr19-35795984;