rs470982

Variant names:

• chr11-134097483-A-G
• rs470982
• NM_032801.5:c.76+28324A>G

Variant summary

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

The NM_032801.5(JAM3):​c.76+28324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,942 control chromosomes in the GnomAD database, including 12,908 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 0.40 (12908 hom., cov: 31)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 3 publications found

Genes affected

JAM3 (HGNC:15532): (junctional adhesion molecule 3) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, the this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions. The encoded protein is a member of the junctional adhesion molecule protein family and acts as a receptor for another member of this family. A mutation in an intron of this gene is associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

JAM3 Gene-Disease associations (from GenCC):

• porencephaly-microcephaly-bilateral congenital cataract syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM3	NM_032801.5	c.76+28324A>G		intron_variant	Intron 1 of 8	ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.76+28324A>G		intron_variant	Intron 1 of 7		NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.76+28324A>G		intron_variant	Intron 1 of 8	1	NM_032801.5	ENSP00000299106.4

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59960 AN: 151824 Hom.: 12882 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.395 AC: 60034 AN: 151942 Hom.: 12908 Cov.: 31 AF XY: 0.395 AC XY: 29305 AN XY: 74250

African (AFR) AF: 0.580 AC: 24008 AN: 41416

American (AMR) AF: 0.319 AC: 4875 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3466

East Asian (EAS) AF: 0.412 AC: 2119 AN: 5140

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4814

European-Finnish (FIN) AF: 0.390 AC: 4119 AN: 10566

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21486 AN: 67950

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.367 Hom.: 1748

Bravo AF: 0.399

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.017
DANN	Benign	0.39
PhyloP100		-0.81
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: rs470982; hg19: chr11-133967378;