dbSNP rs2280307: RHOH:c.-331+15634A>G (chr4-40212934-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004310.5(RHOH):c.-331+15634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,126 control chromosomes in the GnomAD database, including 33,669 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 0.66 ( 33666 hom., cov: 32)

Exomes 𝑓: 0.88 ( 3 hom. )

Consequence

RHOH
NM_004310.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

4 publications found

Variant links:

Genes affected

RHOH (HGNC:686): (ras homolog family member H) The protein encoded by this gene is a member of the Ras superfamily of guanosine triphosphate (GTP)-metabolizing enzymes. The encoded protein is expressed in hematopoietic cells, where it functions as a negative regulator of cell growth and survival. This gene may be hypermutated or misexpressed in leukemias and lymphomas. Chromosomal translocations in non-Hodgkin's lymphoma occur between this locus and B-cell CLL/lymphoma 6 (BCL6) on chromosome 3, leading to the production of fusion transcripts. Alternative splicing in the 5' untranslated region results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2013]

RHOH Gene-Disease associations (from GenCC):

epidermodysplasia verruciformis, susceptibility to, 4
Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
epidermodysplasia verruciformis
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
T-cell immunodeficiency with epidermodysplasia verruciformis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RHOH links:

Genome browser will be placed here

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=-0.93).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOH	NM_004310.5 link	c.-331+15634A>G		intron_variant	Intron 1 of 2	ENST00000381799.10	NP_004301.1	Q15669Q6ICP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOH	ENST00000381799.10 link	c.-331+15634A>G		intron_variant	Intron 1 of 2	1	NM_004310.5	ENSP00000371219.4		Q15669

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100789

AN:

152004

Hom.:

33623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.761

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.659

GnomAD4 exome

AF:

0.875

AC:

AN:

Hom.:

AF XY:

0.875

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.875

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.663

AC:

100886

AN:

152118

Hom.:

33666

Cov.:

AF XY:

0.666

AC XY:

49559

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.623

AC:

25854

AN:

41514

American (AMR)

AF:

0.712

AC:

10882

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

2373

AN:

3468

East Asian (EAS)

AF:

0.666

AC:

3445

AN:

5172

South Asian (SAS)

AF:

0.566

AC:

2720

AN:

4806

European-Finnish (FIN)

AF:

0.761

AC:

8055

AN:

10586

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45414

AN:

67972

Other (OTH)

AF:

0.658

AC:

1386

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1759

3519

5278

7038

8797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.680

Hom.:

12875

Bravo

AF:

0.659

Asia WGS

AF:

0.561

AC:

1951

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0070

(source)

DANN

Benign

0.21

PhyloP100

-1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over