10-30027143-C-G

Variant names:

• chr10-30027143-C-G
• rs3739998
• NM_020848.4:c.3005G>C

Variant summary

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

The NM_020848.4(JCAD):​c.3005G>C​(p.Ser1002Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,950 control chromosomes in the GnomAD database, including 136,854 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (9942 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126912 hom.)
• Consequence: JCAD NM_020848.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 73 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]

ENSG00000304527 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.4336576E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JCAD	NM_020848.4	MANE Select	c.3005G>C	p.Ser1002Thr	missense	Exon 3 of 4	NP_065899.1
	JCAD	NM_001350022.2		c.3005G>C	p.Ser1002Thr	missense	Exon 4 of 5	NP_001336951.1
	JCAD	NM_001350001.2		c.2591G>C	p.Ser864Thr	missense	Exon 4 of 5	NP_001336930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JCAD	ENST00000375377.2	TSL:5 MANE Select	c.3005G>C	p.Ser1002Thr	missense	Exon 3 of 4	ENSP00000364526.1
	ENSG00000304527	ENST00000804350.1		n.-144C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50394 AN: 151984 Hom.: 9938 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.377 AC: 94037 AN: 249440 AF XY: 0.381

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.453

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.410 AC: 598984 AN: 1461848 Hom.: 126912 Cov.: 73 AF XY: 0.409 AC XY: 297784 AN XY: 727228

African (AFR) AF: 0.105 AC: 3504 AN: 33480

American (AMR) AF: 0.429 AC: 19167 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 8658 AN: 26136

East Asian (EAS) AF: 0.165 AC: 6535 AN: 39700

South Asian (SAS) AF: 0.319 AC: 27526 AN: 86258

European-Finnish (FIN) AF: 0.447 AC: 23848 AN: 53398

Middle Eastern (MID) AF: 0.410 AC: 2367 AN: 5768

European-Non Finnish (NFE) AF: 0.435 AC: 484193 AN: 1111992

Other (OTH) AF: 0.384 AC: 23186 AN: 60394

GnomAD4 genome AF: 0.331 AC: 50392 AN: 152102 Hom.: 9942 Cov.: 32 AF XY: 0.335 AC XY: 24928 AN XY: 74344

African (AFR) AF: 0.116 AC: 4810 AN: 41522

American (AMR) AF: 0.422 AC: 6442 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3468

East Asian (EAS) AF: 0.167 AC: 864 AN: 5170

South Asian (SAS) AF: 0.303 AC: 1464 AN: 4832

European-Finnish (FIN) AF: 0.457 AC: 4834 AN: 10570

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29627 AN: 67944

Other (OTH) AF: 0.371 AC: 785 AN: 2116

Alfa AF: 0.410 Hom.: 10048

Bravo AF: 0.320

TwinsUK AF: 0.429 AC: 1589

ALSPAC AF: 0.424 AC: 1636

ESP6500AA AF: 0.119 AC: 454

ESP6500EA AF: 0.425 AC: 3503

ExAC AF: 0.369 AC: 44582

Asia WGS AF: 0.222 AC: 774 AN: 3478

EpiCase AF: 0.436

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.76
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.00024	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.15
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.058
Sift	Benign	0.89	T
Sift4G	Benign	0.68	T
Polyphen		0.058	B
Vest4		0.032
MPC		0.21
ClinPred		0.0023	T
GERP RS		-0.72
Varity_R		0.039
gMVP		0.088
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: rs3739998; hg19: chr10-30316072; COSMIC: COSV64759810;