rs7969431

Positions:

• chr12-93410717-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003348.4(UBE2N):​c.418+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,613,750 control chromosomes in the GnomAD database, including 311 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 0.014 (24 hom., cov: 33)
  • Exomes 𝑓: 0.017 (287 hom.)
• Consequence: UBE2N NM_003348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

Genes affected

UBE2N (HGNC:12492): (ubiquitin conjugating enzyme E2 N) 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, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Studies in mouse suggest that this protein plays a role in DNA postreplication repair. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2194/152334) while in subpopulation NFE AF= 0.0187 (1269/68040). AF 95% confidence interval is 0.0178. There are 24 homozygotes in gnomad4. There are 1089 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2N	NM_003348.4	c.418+17C>T		intron_variant		ENST00000318066.7	NP_003339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2N	ENST00000318066.7	c.418+17C>T		intron_variant		1	NM_003348.4	ENSP00000316176	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2195 AN: 152216 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0150 AC: 3756 AN: 250860 Hom.: 44 AF XY: 0.0152 AC XY: 2054 AN XY: 135544

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00663

Gnomad FIN exome AF: 0.0224

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0169 AC: 24771 AN: 1461416 Hom.: 287 Cov.: 31 AF XY: 0.0169 AC XY: 12302 AN XY: 726972

Gnomad4 AFR exome AF: 0.00332

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0272

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00717

Gnomad4 FIN exome AF: 0.0219

Gnomad4 NFE exome AF: 0.0183

Gnomad4 OTH exome AF: 0.0173

GnomAD4 genome AF: 0.0144 AC: 2194 AN: 152334 Hom.: 24 Cov.: 33 AF XY: 0.0146 AC XY: 1089 AN XY: 74486

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0170 Hom.: 7

Bravo AF: 0.0136

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs7969431; hg19: chr12-93804493;