rs6426514

Positions:

• chr1-228744368-G-A

Variant summary

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

The NM_021205.6(RHOU):​c.*628G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 152,234 control chromosomes in the GnomAD database, including 780 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 0.097 (780 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: RHOU NM_021205.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853

Genes affected

RHOU (HGNC:17794): (ras homolog family member U) This gene encodes a member of the Rho family of GTPases. This protein can activate PAK1 and JNK1, and can induce filopodium formation and stress fiber dissolution. It may also mediate the effects of WNT1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation. A non-coding transcript variant of this gene results from naturally occurring read-through transcription between this locus and the neighboring DUSP5P (dual specificity phosphatase 5 pseudogene) locus.[provided by RefSeq, Mar 2011]

RHOU (HGNC:):

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 = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOU	NM_021205.6	c.*628G>A		3_prime_UTR_variant	3/3	ENST00000366691.4	NP_067028.1
RHOU	NR_037962.1	n.1529G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOU	ENST00000366691.4	c.*628G>A		3_prime_UTR_variant	3/3	1	NM_021205.6	ENSP00000355652.3

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14743 AN: 152100 Hom.: 778 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.125 AC: 2 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0969 AC: 14749 AN: 152218 Hom.: 780 Cov.: 33 AF XY: 0.0935 AC XY: 6962 AN XY: 74440

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0968

Gnomad4 OTH AF: 0.127

Alfa AF: 0.103 Hom.: 864

Bravo AF: 0.103

Asia WGS AF: 0.0410 AC: 143 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	5.9
DANN	Benign	0.35

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: rs6426514; hg19: chr1-228880115;