rs7225527

Variant names:

• chr17-32227931-A-G
• rs7225527
• ENST00000583788.1:n.178T>C

Variant summary

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

The ENST00000583788.1(UBL5P2):​n.178T>C variant causes a non coding transcript exon 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: UBL5P2 ENST00000583788.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 7 publications found

Genes affected

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

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBL5P2		n.32227931A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBL5P2	ENST00000583788.1	n.178T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
RHOT1	ENST00000580392.5	c.359+19622A>G		intron_variant	Intron 3 of 3	3		ENSP00000463532.1
RHOT1	ENST00000584852.1	c.131+16693A>G		intron_variant	Intron 2 of 2	5		ENSP00000461992.1
RHOT1	ENST00000582586.1	n.59-13864A>G		intron_variant	Intron 1 of 1	3

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 v4.3

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;