10-30046193-T-C

Variant names:

• chr10-30046193-T-C
• rs2505083
• NM_020848.4:c.281+1339A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 84 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
JCAD	NM_020848.4	c.281+1339A>G		intron_variant	Intron 2 of 3	ENST00000375377.2	NP_065899.1
JCAD	NM_001350022.2	c.281+1339A>G		intron_variant	Intron 3 of 4		NP_001336951.1
JCAD	NM_001350001.2	c.-174+1339A>G		intron_variant	Intron 2 of 4		NP_001336930.1
JCAD	NM_001350021.2	c.-174+1339A>G		intron_variant	Intron 2 of 4		NP_001336950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JCAD	ENST00000375377.2	c.281+1339A>G		intron_variant	Intron 2 of 3	5	NM_020848.4	ENSP00000364526.1

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

African (AFR) AF: 0.103 AC: 4264 AN: 41456

American (AMR) AF: 0.409 AC: 6244 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3468

East Asian (EAS) AF: 0.191 AC: 985 AN: 5148

South Asian (SAS) AF: 0.332 AC: 1592 AN: 4796

European-Finnish (FIN) AF: 0.469 AC: 4956 AN: 10556

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29523 AN: 67940

Other (OTH) AF: 0.360 AC: 760 AN: 2112

Alfa AF: 0.400 Hom.: 46898

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
PhyloP100		-0.83
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: rs2505083; hg19: chr10-30335122;