rs1071727

Variant names:

• chr12-124911942-T-C
• rs1071727
• NM_021009.7:c.1830A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-124911942-T-C
• chr12-124911942-T-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_021009.7(UBC):​c.1830A>G​(p.Gln610Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (25163 hom., cov: 17)
  • Exomes 𝑓: 0.77 (428748 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.598
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-124911942-T-C is Benign according to our data. Variant chr12-124911942-T-C is described in ClinVar as Benign. ClinVar VariationId is 768597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.598 with no splicing effect.

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.1830A>G	p.Gln610Gln	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.1830A>G	p.Gln610Gln	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.1830A>G	p.Gln610Gln	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.1830A>G	p.Gln610Gln	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 76796 AN: 125442 Hom.: 25150 Cov.: 17

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.754

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.627

GnomAD2 exomes AF: 0.690 AC: 157790 AN: 228794 AF XY: 0.707

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.768

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.723

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.771 AC: 1063272 AN: 1378414 Hom.: 428748 Cov.: 63 AF XY: 0.773 AC XY: 530639 AN XY: 686744

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.434 AC: 13519 AN: 31180

American (AMR) AF: 0.557 AC: 24058 AN: 43188

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 19109 AN: 25254

East Asian (EAS) AF: 0.184 AC: 7138 AN: 38866

South Asian (SAS) AF: 0.759 AC: 62933 AN: 82886

European-Finnish (FIN) AF: 0.656 AC: 34581 AN: 52706

Middle Eastern (MID) AF: 0.782 AC: 4299 AN: 5494

European-Non Finnish (NFE) AF: 0.822 AC: 856074 AN: 1041828

Other (OTH) AF: 0.729 AC: 41561 AN: 57012

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.612 AC: 76843 AN: 125560 Hom.: 25163 Cov.: 17 AF XY: 0.601 AC XY: 36611 AN XY: 60952

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.406 AC: 14195 AN: 34936

American (AMR) AF: 0.578 AC: 7179 AN: 12416

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2177 AN: 2980

East Asian (EAS) AF: 0.198 AC: 928 AN: 4686

South Asian (SAS) AF: 0.662 AC: 2132 AN: 3220

European-Finnish (FIN) AF: 0.601 AC: 5266 AN: 8764

Middle Eastern (MID) AF: 0.736 AC: 184 AN: 250

European-Non Finnish (NFE) AF: 0.773 AC: 43236 AN: 55946

Other (OTH) AF: 0.626 AC: 1022 AN: 1632

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.724 Hom.: 6793

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	-0.68
CADD	Benign	5.7
DANN	Benign	0.85
PhyloP100		0.60
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1071727; hg19: chr12-125396488; COSMIC: COSV60059134; COSMIC: COSV60059134;