rs2054780

Variant names:

• chr1-207048267-C-T
• rs2054780
• NM_018566.4:c.*753G>A

Variant summary

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

The NM_018566.4(YOD1):​c.*753G>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 0.12 in 152,600 control chromosomes in the GnomAD database, including 1,192 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 0.12 (1187 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5 hom.)
• Consequence: YOD1 NM_018566.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 13 publications found

Genes affected

YOD1 (HGNC:25035): (YOD1 deubiquitinase) Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. The protein encoded by this gene belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

PFKFB2 (HGNC:8873): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2) The protein encoded by this gene is involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YOD1	NM_018566.4	c.*753G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000315927.9	NP_061036.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YOD1	ENST00000315927.9	c.*753G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_018566.4	ENSP00000326813.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18268 AN: 152050 Hom.: 1184 Cov.: 32

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.123 AC: 53 AN: 432 Hom.: 5 Cov.: 0 AF XY: 0.0984 AC XY: 25 AN XY: 254

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.128 AC: 53 AN: 414

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.120 AC: 18282 AN: 152168 Hom.: 1187 Cov.: 32 AF XY: 0.122 AC XY: 9107 AN XY: 74410

African (AFR) AF: 0.0703 AC: 2920 AN: 41524

American (AMR) AF: 0.197 AC: 3009 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3466

East Asian (EAS) AF: 0.0748 AC: 388 AN: 5188

South Asian (SAS) AF: 0.111 AC: 537 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1499 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9066 AN: 67992

Other (OTH) AF: 0.143 AC: 303 AN: 2112

Alfa AF: 0.133 Hom.: 2095

Bravo AF: 0.122

Asia WGS AF: 0.0920 AC: 318 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	14
DANN	Benign	0.94
PhyloP100		2.3
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: rs2054780; hg19: chr1-207221612;