Variant 10-30026310-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020848.4(JCAD):c.3838G>A(p.Asp1280Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00137 in 1,614,062 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 22 hom. )

Consequence

JCAD
NM_020848.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.50

Variant links:

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]

JCAD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061148703).

BP6

Variant 10-30026310-C-T is Benign according to our data. Variant chr10-30026310-C-T is described in ClinVar as [Benign]. Clinvar id is 728960.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1135/152314) while in subpopulation AFR AF= 0.0261 (1085/41564). AF 95% confidence interval is 0.0248. There are 14 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
JCAD	NM_020848.4 linkuse as main transcript	c.3838G>A	p.Asp1280Asn	missense_variant	3/4	ENST00000375377.2
JCAD	NM_001350022.2 linkuse as main transcript	c.3838G>A	p.Asp1280Asn	missense_variant	4/5
JCAD	NM_001350001.2 linkuse as main transcript	c.3424G>A	p.Asp1142Asn	missense_variant	4/5
JCAD	NM_001350021.2 linkuse as main transcript	c.3424G>A	p.Asp1142Asn	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JCAD	ENST00000375377.2 linkuse as main transcript	c.3838G>A	p.Asp1280Asn	missense_variant	3/4	5	NM_020848.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1135

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00181

AC:

450

AN:

249242

Hom.:

AF XY:

0.00123

AC XY:

167

AN XY:

135246

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000738

AC:

1079

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

452

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00745

AC:

1135

AN:

152314

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.000917

Hom.:

Bravo

AF:

0.00835

ESP6500AA

AF:

0.0258

AC:

100

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00226

AC:

273

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Benign

0.12

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Uncertain

0.048

Polyphen

1.0

Vest4

0.26

MVP

0.34

MPC

0.31

ClinPred

0.058

GERP RS

4.5

Varity_R

0.30

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over