rs2070628

Positions:

• chr12-124913971-G-A
• chr12-124913971-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021009.7(UBC):​c.-3-197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 814,598 control chromosomes in the GnomAD database, including 364,715 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 0.87 (59138 hom., cov: 32)
  • Exomes 𝑓: 0.95 (305577 hom.)
• Consequence: UBC NM_021009.7 intron
• Scores: Splicing: ADA: 0.00004380
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

Genes affected

UBC (HGNC:12468): (ubiquitin C) This gene represents a ubiquitin gene, ubiquitin C. The encoded protein is a polyubiquitin precursor. Conjugation of ubiquitin monomers or polymers can lead to various effects within a cell, depending on the residues to which ubiquitin is conjugated. Ubiquitination has been associated with protein degradation, DNA repair, cell cycle regulation, kinase modification, endocytosis, and regulation of other cell signaling pathways. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7	c.-3-197C>T		intron_variant		ENST00000339647.6	NP_066289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBC	ENST00000339647.6	c.-3-197C>T		intron_variant		1	NM_021009.7	ENSP00000344818.5

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131860 AN: 152078 Hom.: 59119 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.890

GnomAD4 exome AF: 0.954 AC: 632137 AN: 662402 Hom.: 305577 Cov.: 8 AF XY: 0.955 AC XY: 324166 AN XY: 339400

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.993

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.924

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.936

GnomAD4 genome AF: 0.867 AC: 131922 AN: 152196 Hom.: 59138 Cov.: 32 AF XY: 0.865 AC XY: 64373 AN XY: 74414

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.888

Alfa AF: 0.965 Hom.: 48260

Bravo AF: 0.837

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000044
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070628; hg19: chr12-125398517;