1-228670108-C-T

Variant names:

• chr1-228670108-C-T
• rs765070
• NR_037962.1:n.386+25076C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_037962.1(RHOU):​n.386+25076C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,140 control chromosomes in the GnomAD database, including 28,019 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 0.59 (28019 hom., cov: 32)
• Consequence: RHOU NR_037962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOU	NR_037962.1	n.386+25076C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89189 AN: 152022 Hom.: 27969 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 89282 AN: 152140 Hom.: 28019 Cov.: 32 AF XY: 0.580 AC XY: 43155 AN XY: 74368

African (AFR) AF: 0.823 AC: 34197 AN: 41540

American (AMR) AF: 0.526 AC: 8039 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3304 AN: 5178

South Asian (SAS) AF: 0.529 AC: 2546 AN: 4810

European-Finnish (FIN) AF: 0.394 AC: 4160 AN: 10550

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33048 AN: 67982

Other (OTH) AF: 0.574 AC: 1213 AN: 2114

Alfa AF: 0.524 Hom.: 90296

Bravo AF: 0.607

Asia WGS AF: 0.567 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.35
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765070; hg19: chr1-228805855; COSMIC: COSV70605471;