rs11578216

Positions:

• chr1-228744351-T-A
• chr1-228744351-T-C

Variant summary

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

The NM_021205.6(RHOU):​c.*611T>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 0.155 in 152,386 control chromosomes in the GnomAD database, including 2,094 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 0.15 (2092 hom., cov: 32)
  • Exomes 𝑓: 0.082 (2 hom.)
• Consequence: RHOU NM_021205.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOU	NM_021205.6	c.*611T>A		3_prime_UTR_variant	3/3	ENST00000366691.4
RHOU	NR_037962.1	n.1512T>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOU	ENST00000366691.4	c.*611T>A		3_prime_UTR_variant	3/3	1	NM_021205.6	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23594 AN: 152122 Hom.: 2097 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0822 AC: 12 AN: 146 Hom.: 2 Cov.: 0 AF XY: 0.0778 AC XY: 7 AN XY: 90

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.155 AC: 23586 AN: 152240 Hom.: 2092 Cov.: 32 AF XY: 0.151 AC XY: 11241 AN XY: 74440

Gnomad4 AFR AF: 0.0978

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.146

Alfa AF: 0.102 Hom.: 175

Bravo AF: 0.145

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.73

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: rs11578216; hg19: chr1-228880098;