rs17177789

Variant names:

• chr14-63212991-C-A
• rs17177789
• NM_020663.5:c.178+7944C>A

Variant summary

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

The NM_020663.5(RHOJ):​c.178+7944C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,120 control chromosomes in the GnomAD database, including 3,056 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 0.18 (3056 hom., cov: 32)
• Consequence: RHOJ NM_020663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOJ	NM_020663.5	c.178+7944C>A		intron_variant	Intron 1 of 4	ENST00000316754.8	NP_065714.1
RHOJ	XM_047431613.1	c.178+7944C>A		intron_variant	Intron 1 of 4		XP_047287569.1
RHOJ	XM_011536993.4	c.178+7944C>A		intron_variant	Intron 1 of 3		XP_011535295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOJ	ENST00000316754.8	c.178+7944C>A		intron_variant	Intron 1 of 4	1	NM_020663.5	ENSP00000316729.3
RHOJ	ENST00000555125.1	c.178+7944C>A		intron_variant	Intron 1 of 3	2		ENSP00000451643.1
RHOJ	ENST00000557133.1	n.363+7944C>A		intron_variant	Intron 1 of 1	2
RHOJ	ENST00000557447.5	n.178+7944C>A		intron_variant	Intron 1 of 4	5		ENSP00000451796.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27949 AN: 152002 Hom.: 3057 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 27955 AN: 152120 Hom.: 3056 Cov.: 32 AF XY: 0.180 AC XY: 13375 AN XY: 74358

African (AFR) AF: 0.0618 AC: 2566 AN: 41540

American (AMR) AF: 0.206 AC: 3140 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3466

East Asian (EAS) AF: 0.140 AC: 725 AN: 5174

South Asian (SAS) AF: 0.121 AC: 583 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1948 AN: 10582

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17437 AN: 67954

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.234 Hom.: 7740

Bravo AF: 0.181

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		-0.29
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: rs17177789; hg19: chr14-63679709;