chr1-113651891-A-G

Variant names:

• chr1-113651891-A-G
• rs1230673
• NM_001142782.2:c.2440+685A>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.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
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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.2440+685A>G		intron	N/A	NP_001136254.1	Q5TCQ9-4
	MAGI3	NM_152900.3		c.2440+685A>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.2440+685A>G		intron	N/A	ENSP00000304604.9	Q5TCQ9-4
	MAGI3	ENST00000369617.8	TSL:1	c.2515+685A>G		intron	N/A	ENSP00000358630.4	Q5TCQ9-2
	MAGI3	ENST00000369611.4	TSL:1	c.2440+685A>G		intron	N/A	ENSP00000358624.4	Q5TCQ9-3

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

African (AFR) AF: 0.603 AC: 25021 AN: 41480

American (AMR) AF: 0.257 AC: 3921 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.0756 AC: 392 AN: 5186

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3105 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22291 AN: 67960

Other (OTH) AF: 0.334 AC: 705 AN: 2112

Alfa AF: 0.339 Hom.: 6888

Bravo AF: 0.384

Asia WGS AF: 0.205 AC: 714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.61
PhyloP100		0.60
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: rs1230673; hg19: chr1-114194513;