14-63283297-C-T

Position:

• chr14-63283297-C-T

Variant summary

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

The NM_020663.5(RHOJ):​c.498+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 1,142,398 control chromosomes in the GnomAD database, including 11,549 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 0.19 (5528 hom., cov: 33)
  • Exomes 𝑓: 0.077 (6021 hom.)
• Consequence: RHOJ NM_020663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

Genes affected

RHOJ (HGNC:688): (ras homolog family member J) This gene encodes one of the many small GTP-binding proteins in the Rho family shown to be associated with focal adhesions in endothelial cells (PMID: 21148427, 22103495). The encoded protein is activated by vascular endothelial growth factor and may regulate angiogenesis. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOJ	NM_020663.5	c.498+81C>T		intron_variant		ENST00000316754.8	NP_065714.1
RHOJ	XM_047431613.1	c.498+81C>T		intron_variant			XP_047287569.1
RHOJ	XM_011536993.4	c.333+81C>T		intron_variant			XP_011535295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOJ	ENST00000316754.8	c.498+81C>T		intron_variant		1	NM_020663.5	ENSP00000316729.3
RHOJ	ENST00000557447.5	n.303+2261C>T		intron_variant		5		ENSP00000451796.1
RHOJ	ENST00000555125.1	c.*42C>T		downstream_gene_variant		2		ENSP00000451643.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29185 AN: 152016 Hom.: 5490 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.105 AC: 22239 AN: 211850 Hom.: 2473 AF XY: 0.0958 AC XY: 10949 AN XY: 114304

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.0540

Gnomad ASJ exome AF: 0.0735

Gnomad EAS exome AF: 0.181

Gnomad SAS exome AF: 0.0634

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.0602

Gnomad OTH exome AF: 0.0825

GnomAD4 exome AF: 0.0770 AC: 76231 AN: 990264 Hom.: 6021 Cov.: 13 AF XY: 0.0748 AC XY: 38226 AN XY: 510816

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.0575

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0617

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.0548

Gnomad4 OTH exome AF: 0.0985

GnomAD4 genome AF: 0.193 AC: 29290 AN: 152134 Hom.: 5528 Cov.: 33 AF XY: 0.192 AC XY: 14301 AN XY: 74392

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.159

Alfa AF: 0.142 Hom.: 1009

Bravo AF: 0.201

Asia WGS AF: 0.172 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.38

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: rs2179967; hg19: chr14-63750015;