NM_002361.4:c.1231+2373C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_002361.4(MAG):​c.1231+2373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 152,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00020 (0 hom., cov: 32)
• Consequence: MAG NM_002361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000197 (30/152218) while in subpopulation AFR AF= 0.000506 (21/41516). AF 95% confidence interval is 0.000338. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

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

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74418

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.41

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: rs7249617; hg19: chr19-35795984;