1-154552497-A-G

Variant names:

• chr1-154552497-A-G
• rs12144146
• NM_017582.7:c.815-33T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017582.7(UBE2Q1):​c.815-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,124 control chromosomes in the GnomAD database, including 66,534 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 0.21 (4516 hom., cov: 33)
  • Exomes 𝑓: 0.28 (62018 hom.)
• Consequence: UBE2Q1 NM_017582.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 10 publications found

Genes affected

UBE2Q1 (HGNC:15698): (ubiquitin conjugating enzyme E2 Q1) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is 98% identical to the mouse counterpart. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017582.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2Q1	NM_017582.7	MANE Select	c.815-33T>C		intron	N/A	NP_060052.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2Q1	ENST00000292211.5	TSL:1 MANE Select	c.815-33T>C		intron	N/A	ENSP00000292211.4
	UBE2Q1	ENST00000483639.1	TSL:3	n.369T>C		non_coding_transcript_exon	Exon 2 of 6
	UBE2Q1	ENST00000718442.1		c.308-33T>C		intron	N/A	ENSP00000520827.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32526 AN: 152148 Hom.: 4518 Cov.: 33

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.234 AC: 58756 AN: 250864 AF XY: 0.237

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.00647

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.281 AC: 411025 AN: 1460858 Hom.: 62018 Cov.: 33 AF XY: 0.278 AC XY: 202327 AN XY: 726692

African (AFR) AF: 0.0476 AC: 1592 AN: 33464

American (AMR) AF: 0.245 AC: 10949 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6515 AN: 26096

East Asian (EAS) AF: 0.0225 AC: 895 AN: 39694

South Asian (SAS) AF: 0.152 AC: 13127 AN: 86146

European-Finnish (FIN) AF: 0.288 AC: 15355 AN: 53404

Middle Eastern (MID) AF: 0.208 AC: 1201 AN: 5766

European-Non Finnish (NFE) AF: 0.312 AC: 346272 AN: 1111258

Other (OTH) AF: 0.250 AC: 15119 AN: 60362

GnomAD4 genome AF: 0.214 AC: 32523 AN: 152266 Hom.: 4516 Cov.: 33 AF XY: 0.211 AC XY: 15682 AN XY: 74452

African (AFR) AF: 0.0553 AC: 2297 AN: 41566

American (AMR) AF: 0.256 AC: 3916 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3468

East Asian (EAS) AF: 0.0146 AC: 76 AN: 5194

South Asian (SAS) AF: 0.141 AC: 679 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3085 AN: 10606

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20688 AN: 67998

Other (OTH) AF: 0.225 AC: 475 AN: 2110

Alfa AF: 0.262 Hom.: 1768

Bravo AF: 0.205

Asia WGS AF: 0.0720 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.59
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs12144146; hg19: chr1-154524973; COSMIC: COSV52727535; COSMIC: COSV52727535;