rs1108718

Positions:

• chr3-65818908-G-A

Variant summary

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

The NM_001033057.2(MAGI1):​c.314-196820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,976 control chromosomes in the GnomAD database, including 18,718 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 0.48 (18718 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.314-196820C>T		intron_variant		ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.314-196820C>T		intron_variant		1	NM_001033057.2	ENSP00000385450	A2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72543 AN: 151858 Hom.: 18728 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.477 AC: 72553 AN: 151976 Hom.: 18718 Cov.: 32 AF XY: 0.482 AC XY: 35851 AN XY: 74308

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.475

Alfa AF: 0.536 Hom.: 36184

Bravo AF: 0.472

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46

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: rs1108718; hg19: chr3-65804583;