rs1230661

Variant names:

• chr1-113642968-A-G
• rs1230661
• NM_001142782.2:c.1966+452A>G

Variant summary

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

The NM_001142782.2(MAGI3):​c.1966+452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,232 control chromosomes in the GnomAD database, including 50,600 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 0.81 (50600 hom., cov: 34)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142782.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.1966+452A>G		intron	N/A	NP_001136254.1	Q5TCQ9-4
	MAGI3	NM_152900.3		c.1966+452A>G		intron	N/A	NP_690864.2	Q5TCQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.1966+452A>G		intron	N/A	ENSP00000304604.9	Q5TCQ9-4
	MAGI3	ENST00000369617.8	TSL:1	c.2041+452A>G		intron	N/A	ENSP00000358630.4	Q5TCQ9-2
	MAGI3	ENST00000369611.4	TSL:1	c.1966+452A>G		intron	N/A	ENSP00000358624.4	Q5TCQ9-3

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122648 AN: 152114 Hom.: 50540 Cov.: 34

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.806 AC: 122767 AN: 152232 Hom.: 50600 Cov.: 34 AF XY: 0.801 AC XY: 59589 AN XY: 74418

African (AFR) AF: 0.956 AC: 39741 AN: 41576

American (AMR) AF: 0.734 AC: 11213 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2778 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1946 AN: 5174

South Asian (SAS) AF: 0.818 AC: 3946 AN: 4826

European-Finnish (FIN) AF: 0.695 AC: 7352 AN: 10582

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53137 AN: 68006

Other (OTH) AF: 0.782 AC: 1651 AN: 2110

Alfa AF: 0.783 Hom.: 41699

Bravo AF: 0.807

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.69
PhyloP100		0.012
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: rs1230661; hg19: chr1-114185590;