3-65500713-A-G

Variant names:

• chr3-65500713-A-G
• rs1524976
• NM_001033057.2:c.431-7082T>C

Variant summary

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

The NM_001033057.2(MAGI1):​c.431-7082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,232 control chromosomes in the GnomAD database, including 56,658 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 0.86 (56658 hom., cov: 33)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.431-7082T>C		intron_variant	Intron 2 of 22	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.431-7082T>C		intron_variant	Intron 2 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131156 AN: 152114 Hom.: 56629 Cov.: 33

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.862 AC: 131235 AN: 152232 Hom.: 56658 Cov.: 33 AF XY: 0.863 AC XY: 64246 AN XY: 74424

African (AFR) AF: 0.867 AC: 36010 AN: 41528

American (AMR) AF: 0.893 AC: 13648 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2732 AN: 3472

East Asian (EAS) AF: 0.967 AC: 5008 AN: 5178

South Asian (SAS) AF: 0.883 AC: 4258 AN: 4822

European-Finnish (FIN) AF: 0.840 AC: 8910 AN: 10604

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57996 AN: 68020

Other (OTH) AF: 0.847 AC: 1791 AN: 2114

Alfa AF: 0.856 Hom.: 102116

Bravo AF: 0.866

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.63
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1524976; hg19: chr3-65486388;