rs264704

Variant names:

• chr3-65878781-T-C
• rs264704
• NM_001033057.2:c.313+159215A>G

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+159215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 152,176 control chromosomes in the GnomAD database, including 1,938 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 0.089 (1938 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 0 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.313+159215A>G		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+159215A>G		intron_variant	Intron 1 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13422 AN: 152058 Hom.: 1927 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0885 AC: 13475 AN: 152176 Hom.: 1938 Cov.: 32 AF XY: 0.0852 AC XY: 6342 AN XY: 74428

African (AFR) AF: 0.300 AC: 12454 AN: 41466

American (AMR) AF: 0.0337 AC: 515 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 203 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00207 AC: 141 AN: 68030

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0697 Hom.: 416

Bravo AF: 0.102

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.97
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: rs264704; hg19: chr3-65864456;