chr1-228744351-T-A

Variant names:

• chr1-228744351-T-A
• rs11578216
• NM_021205.6:c.*611T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021205.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOU	NM_021205.6	MANE Select	c.*611T>A		3_prime_UTR	Exon 3 of 3	NP_067028.1
	RHOU	NR_037962.1		n.1512T>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOU	ENST00000366691.4	TSL:1 MANE Select	c.*611T>A		3_prime_UTR	Exon 3 of 3	ENSP00000355652.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0938 AC: 12 AN: 128

Other (OTH) AF: 0.00 AC: 0 AN: 8

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

African (AFR) AF: 0.0978 AC: 4065 AN: 41546

American (AMR) AF: 0.109 AC: 1661 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3472

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5190

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4830

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13728 AN: 68004

Other (OTH) AF: 0.146 AC: 309 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11578216; hg19: chr1-228880098;