chr14-63283297-C-A

Variant names:

• chr14-63283297-C-A
• rs2179967
• NM_020663.5:c.498+81C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020663.5(RHOJ):​c.498+81C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RHOJ NM_020663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOJ	NM_020663.5	c.498+81C>A		intron_variant	Intron 4 of 4	ENST00000316754.8	NP_065714.1
RHOJ	XM_047431613.1	c.498+81C>A		intron_variant	Intron 4 of 4		XP_047287569.1
RHOJ	XM_011536993.4	c.333+81C>A		intron_variant	Intron 3 of 3		XP_011535295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOJ	ENST00000316754.8	c.498+81C>A		intron_variant	Intron 4 of 4	1	NM_020663.5	ENSP00000316729.3
RHOJ	ENST00000557447.5	n.303+2261C>A		intron_variant	Intron 3 of 4	5		ENSP00000451796.1
RHOJ	ENST00000555125.1	c.*42C>A		downstream_gene_variant		2		ENSP00000451643.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152046 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 990804 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 511030

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24506

American (AMR) AF: 0.00 AC: 0 AN: 41338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22976

East Asian (EAS) AF: 0.00 AC: 0 AN: 37390

South Asian (SAS) AF: 0.00 AC: 0 AN: 75216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4934

European-Non Finnish (NFE) AF: 0.00000144 AC: 1 AN: 696146

Other (OTH) AF: 0.00 AC: 0 AN: 45218

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152046 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0010
DANN	Benign	0.42
PhyloP100		-2.2

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: rs2179967; hg19: chr14-63750015;