Genetic Variant RHOJ:c.498+81C>T (chr14-63283297-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23

Publications

4 publications found

Variant links:

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]

RHOJ links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020663.5. 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
	RHOJ	NM_020663.5	MANE Select	c.498+81C>T		intron	N/A	NP_065714.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RHOJ	ENST00000316754.8	TSL:1 MANE Select	c.498+81C>T	intron	N/A	ENSP00000316729.3
RHOJ	ENST00000557447.5	TSL:5	n.303+2261C>T	intron	N/A	ENSP00000451796.1
RHOJ	ENST00000555125.1	TSL:2	c.*42C>T	downstream_gene	N/A	ENSP00000451643.1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29185

AN:

152016

Hom.:

5490

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.105

AC:

22239

AN:

211850

AF XY:

0.0958

show subpopulations

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 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.:

AF XY:

0.0748

AC XY:

38226

AN XY:

510816

show subpopulations

African (AFR)

AF:

0.503

AC:

12295

AN:

24460

American (AMR)

AF:

0.0575

AC:

2376

AN:

41330

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1732

AN:

22968

East Asian (EAS)

AF:

0.162

AC:

6066

AN:

37380

South Asian (SAS)

AF:

0.0617

AC:

4642

AN:

75192

European-Finnish (FIN)

AF:

0.144

AC:

6219

AN:

43058

Middle Eastern (MID)

AF:

0.0602

AC:

297

AN:

4930

European-Non Finnish (NFE)

AF:

0.0548

AC:

38153

AN:

695758

Other (OTH)

AF:

0.0985

AC:

4451

AN:

45188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3326

6652

9978

13304

16630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1256

2512

3768

5024

6280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.193

AC:

29290

AN:

152134

Hom.:

5528

Cov.:

AF XY:

0.192

AC XY:

14301

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.491

AC:

20355

AN:

41470

American (AMR)

AF:

0.0899

AC:

1374

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3468

East Asian (EAS)

AF:

0.168

AC:

869

AN:

5170

South Asian (SAS)

AF:

0.0702

AC:

339

AN:

4828

European-Finnish (FIN)

AF:

0.156

AC:

1657

AN:

10596

Middle Eastern (MID)

AF:

0.0925

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0591

AC:

4022

AN:

67998

Other (OTH)

AF:

0.159

AC:

336

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

927

1853

2780

3706

4633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

1135

Bravo

AF:

0.201

Asia WGS

AF:

0.172

AC:

595

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0020

(source)

DANN

Benign

0.38

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over