rs1230673

chr1-113651891-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142782.2(MAGI3):c.2440+685A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,070 control chromosomes in the GnomAD database, including 12,922 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 0.38 (12922 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

Genes affected

MAGI3 (HGNC:29647): (membrane associated guanylate kinase, WW and PDZ domain containing 3) Predicted to enable frizzled binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within positive regulation of JUN kinase activity. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI3	NM_001142782.2	c.2440+685A>G		intron_variant		ENST00000307546.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI3	ENST00000307546.14	c.2440+685A>G		intron_variant		5	NM_001142782.2
MAGI3	ENST00000369611.4	c.2440+685A>G		intron_variant		1		P1
MAGI3	ENST00000369617.8	c.2515+685A>G		intron_variant		1
MAGI3	ENST00000369615.5	c.2440+685A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58153 AN: 151952 Hom.: 12890 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0754

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.383 AC: 58240 AN: 152070 Hom.: 12922 Cov.: 32 AF XY: 0.376 AC XY: 27949 AN XY: 74338

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.0756

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.334

Alfa AF: 0.341 Hom.: 4779

Bravo AF: 0.384

Asia WGS AF: 0.205 AC: 714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.4
Dann	Benign	0.61

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: rs1230673; hg19: chr1-114194513;