10-30046193-T-C

Variant summary

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

The NM_020848.4(JCAD):c.281+1339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,952 control chromosomes in the GnomAD database, including 9,894 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 0.33 (9894 hom., cov: 31)
• Consequence: JCAD NM_020848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

Genes affected

JCAD (HGNC:29283): (junctional cadherin 5 associated) This gene encodes an endothelial cell-to-cell junction protein. Naturally occurring mutations in this gene are associated with coronary artery disease, late onset alzheimer disease, and emphysema distribution. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JCAD	NM_020848.4	c.281+1339A>G		intron_variant		ENST00000375377.2
JCAD	NM_001350001.2	c.-174+1339A>G		intron_variant
JCAD	NM_001350021.2	c.-174+1339A>G		intron_variant
JCAD	NM_001350022.2	c.281+1339A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JCAD	ENST00000375377.2	c.281+1339A>G		intron_variant		5	NM_020848.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49886 AN: 151834 Hom.: 9892 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.328 AC: 49876 AN: 151952 Hom.: 9894 Cov.: 31 AF XY: 0.333 AC XY: 24742 AN XY: 74274

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.360

Alfa AF: 0.411 Hom.: 22913

Bravo AF: 0.313

Asia WGS AF: 0.237 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.16
Dann	Benign	0.63

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: rs2505083; hg19: chr10-30335122;