rs34260

Positions:

• chr12-109113703-G-A
• chr12-109113703-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000541704.2(ENSG00000256139):​n.576+288G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,140 control chromosomes in the GnomAD database, including 23,633 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 0.54 (23633 hom., cov: 33)
• Consequence: ENST00000541704.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44

Genes affected

(HGNC:):

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001412734.1	c.-10+288G>A		intron_variant
ACACB	NM_001412737.1	c.26+288G>A		intron_variant
ACACB	XM_011538263.4	c.-10+288G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000541704.2	n.576+288G>A		intron_variant, non_coding_transcript_variant		5
UNG	ENST00000699563.1	c.774+10092G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81527 AN: 152022 Hom.: 23588 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81625 AN: 152140 Hom.: 23633 Cov.: 33 AF XY: 0.537 AC XY: 39954 AN XY: 74396

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.509

Alfa AF: 0.488 Hom.: 4041

Bravo AF: 0.539

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34260; hg19: chr12-109551508;