rs7649739

Variant names:

• chr3-65413223-G-A
• rs7649739
• NM_001033057.2:c.2168-11753C>T

Variant summary

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

The NM_001033057.2(MAGI1):​c.2168-11753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,032 control chromosomes in the GnomAD database, including 35,463 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 0.68 (35463 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.2168-11753C>T		intron_variant	Intron 12 of 22	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.2168-11753C>T		intron_variant	Intron 12 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102813 AN: 151914 Hom.: 35435 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.677 AC: 102895 AN: 152032 Hom.: 35463 Cov.: 32 AF XY: 0.670 AC XY: 49787 AN XY: 74312

African (AFR) AF: 0.820 AC: 34026 AN: 41484

American (AMR) AF: 0.642 AC: 9805 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2266 AN: 3464

East Asian (EAS) AF: 0.525 AC: 2712 AN: 5162

South Asian (SAS) AF: 0.546 AC: 2633 AN: 4818

European-Finnish (FIN) AF: 0.585 AC: 6176 AN: 10564

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43038 AN: 67962

Other (OTH) AF: 0.653 AC: 1377 AN: 2108

Alfa AF: 0.648 Hom.: 60546

Bravo AF: 0.690

Asia WGS AF: 0.553 AC: 1922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.29
PhyloP100		0.38
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: rs7649739; hg19: chr3-65398898;