chr1-207044014-T-C

Variant names:

• chr1-207044014-T-C
• rs1044145
• NM_018566.4:c.*5006A>G

Variant summary

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

The NM_018566.4(YOD1):​c.*5006A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,426 control chromosomes in the GnomAD database, including 30,033 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 0.61 (29982 hom., cov: 32)
  • Exomes 𝑓: 0.48 (51 hom.)
• Consequence: YOD1 NM_018566.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YOD1	NM_018566.4	c.*5006A>G		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.*5006A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_018566.4	ENSP00000326813.4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92753 AN: 151900 Hom.: 29938 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.483 AC: 197 AN: 408 Hom.: 51 Cov.: 0 AF XY: 0.463 AC XY: 114 AN XY: 246

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: 0.483 AC: 194 AN: 402

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.611 AC: 92856 AN: 152018 Hom.: 29982 Cov.: 32 AF XY: 0.605 AC XY: 44957 AN XY: 74290

African (AFR) AF: 0.814 AC: 33793 AN: 41528

American (AMR) AF: 0.559 AC: 8545 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2236 AN: 3464

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5180

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 6017 AN: 10550

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37125 AN: 67888

Other (OTH) AF: 0.633 AC: 1335 AN: 2108

Alfa AF: 0.574 Hom.: 12604

Bravo AF: 0.621

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.4
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: rs1044145; hg19: chr1-207217359; COSMIC: COSV60006631;