4-40197226-G-C

Position:

• chr4-40197226-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000381799.10(RHOH):​c.-405G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,126 control chromosomes in the GnomAD database, including 36,481 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 0.69 (36480 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: RHOH ENST00000381799.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOH	NM_004310.5	c.-405G>C		5_prime_UTR_variant	1/3	ENST00000381799.10	NP_004301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOH	ENST00000381799.10	c.-405G>C		5_prime_UTR_variant	1/3	1	NM_004310.5	ENSP00000371219	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104955 AN: 152006 Hom.: 36443 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.691 AC: 105044 AN: 152124 Hom.: 36480 Cov.: 33 AF XY: 0.691 AC XY: 51385 AN XY: 74360

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.658

Alfa AF: 0.603 Hom.: 1725

Bravo AF: 0.685

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
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

Other links and lift over

dbSNP: rs2245466; hg19: chr4-40198846;