dbSNP rs61731758: RHOH:p.Ala170Ala (chr4-40243896-C-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004310.5(RHOH):c.510C>G(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,102 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A170A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

RHOH
NM_004310.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.90

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-40243896-C-G is Benign according to our data. Variant chr4-40243896-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 544156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.89 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOH	NM_004310.5 link	c.510C>G	p.Ala170Ala	synonymous_variant	Exon 3 of 3	ENST00000381799.10	NP_004301.1	Q15669Q6ICP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOH	ENST00000381799.10 link	c.510C>G	p.Ala170Ala	synonymous_variant	Exon 3 of 3	1	NM_004310.5	ENSP00000371219.4		Q15669

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

152

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00152

AC:

381

AN:

250332

Hom.:

AF XY:

0.00168

AC XY:

227

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.000680

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.000709

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00111

AC:

1625

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

890

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.000666

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.000998

AC:

152

AN:

152262

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00118

EpiCase

AF:

0.00120

EpiControl

AF:

0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RHOH: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

T-cell immunodeficiency with epidermodysplasia verruciformis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.13

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over