rs264668

Variant names:

• chr3-65893570-C-T
• rs264668
• NM_001033057.2:c.313+144426G>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.313+144426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,038 control chromosomes in the GnomAD database, including 6,405 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 0.24 (6405 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 4 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]

MAGI1-IT1 (HGNC:42436): (MAGI1 intronic transcript 1)

MAGI1-AS1 (HGNC:40091): (MAGI1 antisense RNA 1)

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 = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.313+144426G>A		intron_variant	Intron 1 of 22	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.313+144426G>A		intron_variant	Intron 1 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36150 AN: 151920 Hom.: 6374 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.238 AC: 36231 AN: 152038 Hom.: 6405 Cov.: 32 AF XY: 0.231 AC XY: 17184 AN XY: 74312

African (AFR) AF: 0.498 AC: 20645 AN: 41444

American (AMR) AF: 0.150 AC: 2293 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3472

East Asian (EAS) AF: 0.108 AC: 561 AN: 5172

South Asian (SAS) AF: 0.160 AC: 771 AN: 4826

European-Finnish (FIN) AF: 0.0894 AC: 945 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9679 AN: 67976

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.171 Hom.: 5259

Bravo AF: 0.252

Asia WGS AF: 0.186 AC: 648 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs264668; hg19: chr3-65879245;