rs7225527

Variant names:

• chr17-32227931-A-G
• rs7225527
• ENST00000580392.5:c.359+19622A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000580392.5(RHOT1):​c.359+19622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 963,584 control chromosomes in the GnomAD database, including 16,887 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 0.18 (2578 hom., cov: 29)
  • Exomes 𝑓: 0.18 (14309 hom.)
• Consequence: RHOT1 ENST00000580392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 7 publications found

Genes affected

RHOT1 (HGNC:21168): (ras homolog family member T1) Predicted to enable GTP binding activity and GTPase activity. Involved in cellular homeostasis; mitochondrial outer membrane permeabilization; and mitochondrion transport along microtubule. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

UBL5P2 (HGNC:44640): (ubiquitin like 5 pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000580392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT1	ENST00000580392.5	TSL:3	c.359+19622A>G		intron	N/A	ENSP00000463532.1	J3QLG2
	RHOT1	ENST00000584852.1	TSL:5	c.131+16693A>G		intron	N/A	ENSP00000461992.1	J3KRG7
	UBL5P2	ENST00000583788.1	TSL:6	n.178T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27441 AN: 151632 Hom.: 2571 Cov.: 29

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.180 AC: 146036 AN: 811834 Hom.: 14309 Cov.: 11 AF XY: 0.184 AC XY: 79068 AN XY: 428730

African (AFR) AF: 0.177 AC: 3669 AN: 20754

American (AMR) AF: 0.240 AC: 10230 AN: 42708

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4191 AN: 20900

East Asian (EAS) AF: 0.216 AC: 7489 AN: 34724

South Asian (SAS) AF: 0.279 AC: 20468 AN: 73398

European-Finnish (FIN) AF: 0.142 AC: 7015 AN: 49352

Middle Eastern (MID) AF: 0.219 AC: 953 AN: 4342

European-Non Finnish (NFE) AF: 0.161 AC: 85130 AN: 528026

Other (OTH) AF: 0.183 AC: 6891 AN: 37630

GnomAD4 genome AF: 0.181 AC: 27471 AN: 151750 Hom.: 2578 Cov.: 29 AF XY: 0.181 AC XY: 13382 AN XY: 74136

African (AFR) AF: 0.183 AC: 7572 AN: 41366

American (AMR) AF: 0.185 AC: 2811 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1151 AN: 5154

South Asian (SAS) AF: 0.273 AC: 1312 AN: 4798

European-Finnish (FIN) AF: 0.138 AC: 1454 AN: 10520

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11871 AN: 67908

Other (OTH) AF: 0.183 AC: 385 AN: 2106

Alfa AF: 0.179 Hom.: 319

Bravo AF: 0.184

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.3
DANN	Benign	0.89
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7225527; hg19: chr17-30554950; COSMIC: COSV61715972;