rs17840844

Variant names:

• chr12-124912515-G-A
• rs17840844
• NM_021009.7:c.1257C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021009.7(UBC):​c.1257C>T​(p.Asp419Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,155,828 control chromosomes in the GnomAD database, including 146,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (1241 hom., cov: 5)
  • Exomes 𝑓: 0.55 (146306 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.218
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-124912515-G-A is Benign according to our data. Variant chr12-124912515-G-A is described in ClinVar as Benign. ClinVar VariationId is 768598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.218 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 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.1257C>T	p.Asp419Asp	synonymous	Exon 2 of 2	NP_066289.3	P0CG48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	ENST00000339647.6	TSL:1 MANE Select	c.1257C>T	p.Asp419Asp	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.1257C>T	p.Asp419Asp	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.1257C>T	p.Asp419Asp	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 7288 AN: 19628 Hom.: 1241 Cov.: 5

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.508 AC: 121638 AN: 239638 AF XY: 0.526

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.548 AC: 633607 AN: 1155828 Hom.: 146306 Cov.: 28 AF XY: 0.552 AC XY: 322968 AN XY: 585496

African (AFR) AF: 0.208 AC: 6201 AN: 29786

American (AMR) AF: 0.424 AC: 18366 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 11938 AN: 23692

East Asian (EAS) AF: 0.177 AC: 6843 AN: 38632

South Asian (SAS) AF: 0.567 AC: 44182 AN: 77862

European-Finnish (FIN) AF: 0.523 AC: 27138 AN: 51876

Middle Eastern (MID) AF: 0.540 AC: 2593 AN: 4798

European-Non Finnish (NFE) AF: 0.587 AC: 490420 AN: 835670

Other (OTH) AF: 0.516 AC: 25926 AN: 50226

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.370 AC: 7304 AN: 19744 Hom.: 1241 Cov.: 5 AF XY: 0.375 AC XY: 3895 AN XY: 10380

African (AFR) AF: 0.146 AC: 741 AN: 5074

American (AMR) AF: 0.379 AC: 943 AN: 2488

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 185 AN: 454

East Asian (EAS) AF: 0.136 AC: 107 AN: 786

South Asian (SAS) AF: 0.539 AC: 166 AN: 308

European-Finnish (FIN) AF: 0.414 AC: 984 AN: 2374

Middle Eastern (MID) AF: 0.423 AC: 22 AN: 52

European-Non Finnish (NFE) AF: 0.512 AC: 4049 AN: 7914

Other (OTH) AF: 0.342 AC: 78 AN: 228

Alfa AF: 0.443 Hom.: 981

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.94
PhyloP100		0.22
Mutation Taster		=92/8	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: rs17840844; hg19: chr12-125397061; COSMIC: COSV60058155; COSMIC: COSV60058155;