rs2070628

Variant names:

• chr12-124913971-G-A
• rs2070628
• NM_021009.7:c.-3-197C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021009.7. 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
	UBC	NM_021009.7	MANE Select	c.-3-197C>T		intron	N/A	NP_066289.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	ENST00000339647.6	TSL:1 MANE Select	c.-3-197C>T		intron	N/A	ENSP00000344818.5
	UBC	ENST00000540351.1	TSL:1	c.-4+34C>T		intron	N/A	ENSP00000442800.1
	UBC	ENST00000536769.1	TSL:6	c.-200C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000441543.1

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

African (AFR) AF: 0.661 AC: 10592 AN: 16036

American (AMR) AF: 0.719 AC: 13200 AN: 18358

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 14685 AN: 14794

East Asian (EAS) AF: 0.598 AC: 18796 AN: 31416

South Asian (SAS) AF: 0.924 AC: 44523 AN: 48160

European-Finnish (FIN) AF: 0.997 AC: 28780 AN: 28866

Middle Eastern (MID) AF: 0.973 AC: 2313 AN: 2376

European-Non Finnish (NFE) AF: 0.998 AC: 468553 AN: 469608

Other (OTH) AF: 0.936 AC: 30695 AN: 32788

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

African (AFR) AF: 0.666 AC: 27624 AN: 41462

American (AMR) AF: 0.773 AC: 11821 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3439 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3219 AN: 5174

South Asian (SAS) AF: 0.904 AC: 4366 AN: 4828

European-Finnish (FIN) AF: 0.995 AC: 10570 AN: 10622

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67807 AN: 68022

Other (OTH) AF: 0.888 AC: 1880 AN: 2116

Alfa AF: 0.944 Hom.: 64329

Bravo AF: 0.837

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.68
PhyloP100		0.18
PromoterAI		-0.0087	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070628; hg19: chr12-125398517;