4-40212934-A-G

Position:

• chr4-40212934-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.93).
• 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/exons	MANE	UniProt
RHOH	NM_004310.5	c.-331+15634A>G		intron_variant		ENST00000381799.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOH	ENST00000381799.10	c.-331+15634A>G		intron_variant		1	NM_004310.5	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100789 AN: 152004 Hom.: 33623 Cov.: 32

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: 7 AN: 8 Hom.: 3 AF XY: 0.875 AC XY: 7 AN XY: 8

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.663 AC: 100886 AN: 152118 Hom.: 33666 Cov.: 32 AF XY: 0.666 AC XY: 49559 AN XY: 74364

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.658

Alfa AF: 0.680 Hom.: 8809

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
DANN	Benign	0.21

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: rs2280307; hg19: chr4-40214554;