Variant chr12-124912698-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021009.7(UBC):c.1074T>C(p.Arg358Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,599,596 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 18 hom., cov: 25)

Exomes 𝑓: 0.0057 ( 128 hom. )

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.301

Variant links:

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]

UBC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-124912698-A-G is Benign according to our data. Variant chr12-124912698-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 776776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.301 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1738/138430) while in subpopulation AFR AF= 0.0288 (1053/36594). AF 95% confidence interval is 0.0273. There are 18 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1738 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.1074T>C	p.Arg358Arg	synonymous_variant	2/2	ENST00000339647.6	NP_066289.3	P0CG48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBC	ENST00000339647.6 linkuse as main transcript	c.1074T>C	p.Arg358Arg	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.1074T>C	p.Arg358Arg	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.452-518T>C		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1740

AN:

138342

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0359

Gnomad EAS

AF:

0.000218

Gnomad SAS

AF:

0.00215

Gnomad FIN

AF:

0.000222

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.00487

Gnomad OTH

AF:

0.0195

GnomAD3 exomes

AF:

0.00801

AC:

2012

AN:

251044

Hom.:

AF XY:

0.00727

AC XY:

987

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.0307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.00569

AC:

8314

AN:

1461166

Hom.:

128

Cov.:

AF XY:

0.00556

AC XY:

4041

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00442

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.0126

AC:

1738

AN:

138430

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

837

AN XY:

67278

show subpopulations

Gnomad4 AFR

AF:

0.0288

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0359

Gnomad4 EAS

AF:

0.000218

Gnomad4 SAS

AF:

0.00216

Gnomad4 FIN

AF:

0.000222

Gnomad4 NFE

AF:

0.00487

Gnomad4 OTH

AF:

0.0193

Alfa

AF:

0.0107

Hom.:

EpiCase

AF:

0.00600

EpiControl

AF:

0.00836

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 14, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2022	See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.0

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over