rs1524962

Variant names:

• chr3-65599006-C-T
• rs1524962
• NM_001033057.2:c.430+22966G>A

Variant summary

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

The NM_001033057.2(MAGI1):​c.430+22966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,156 control chromosomes in the GnomAD database, including 4,090 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 0.22 (4090 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 7 publications found

Genes affected

MAGI1 (HGNC:946): (membrane associated guanylate kinase, WW and PDZ domain containing 1) The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033057.2. 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
	MAGI1	NM_001033057.2	MANE Select	c.430+22966G>A		intron	N/A	NP_001028229.1	Q96QZ7-2
	MAGI1	NM_001365903.2		c.430+22966G>A		intron	N/A	NP_001352832.1
	MAGI1	NM_001365904.2		c.430+22966G>A		intron	N/A	NP_001352833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI1	ENST00000402939.7	TSL:1 MANE Select	c.430+22966G>A		intron	N/A	ENSP00000385450.2	Q96QZ7-2
	MAGI1	ENST00000330909.12	TSL:1	c.430+22966G>A		intron	N/A	ENSP00000331157.7	Q96QZ7-5
	MAGI1	ENST00000483466.5	TSL:1	c.430+22966G>A		intron	N/A	ENSP00000420323.1	Q96QZ7-3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33647 AN: 152038 Hom.: 4086 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.221 AC: 33666 AN: 152156 Hom.: 4090 Cov.: 32 AF XY: 0.215 AC XY: 16015 AN XY: 74390

African (AFR) AF: 0.190 AC: 7888 AN: 41518

American (AMR) AF: 0.182 AC: 2785 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4830

European-Finnish (FIN) AF: 0.272 AC: 2877 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18275 AN: 67978

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.250 Hom.: 8732

Bravo AF: 0.214

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		-0.0040
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: rs1524962; hg19: chr3-65584681;