rs1018784

Variant names:

• chr12-109098211-C-T
• rs1018784
• ENST00000446767.2:n.-116C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000446767.2(UNG):​n.-116C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,454,230 control chromosomes in the GnomAD database, including 770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (462 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (308 hom.)
• Consequence: UNG ENST00000446767.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.262
• Publications: 4 publications found

Genes affected

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]

UNG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-109098211-C-T is Benign according to our data. Variant chr12-109098211-C-T is described in ClinVar as Benign. ClinVar VariationId is 1251149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446767.2. 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
	UNG	NM_080911.3	MANE Select	c.133-221C>T		intron	N/A	NP_550433.1
	UNG	NM_003362.4		c.-116C>T		5_prime_UTR	Exon 1 of 6	NP_003353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000446767.2	TSL:1	n.-116C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000400287.2
	UNG	ENST00000336865.6	TSL:1	c.-116C>T		5_prime_UTR	Exon 1 of 6	ENSP00000337398.2
	UNG	ENST00000446767.2	TSL:1	n.-116C>T		5_prime_UTR	Exon 1 of 5	ENSP00000400287.2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6352 AN: 152242 Hom.: 461 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.00384 AC: 4994 AN: 1301870 Hom.: 308 Cov.: 33 AF XY: 0.00339 AC XY: 2144 AN XY: 633250

African (AFR) AF: 0.141 AC: 4110 AN: 29052

American (AMR) AF: 0.00972 AC: 225 AN: 23156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19128

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36464

South Asian (SAS) AF: 0.000280 AC: 18 AN: 64320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31984

Middle Eastern (MID) AF: 0.00389 AC: 14 AN: 3596

European-Non Finnish (NFE) AF: 0.000175 AC: 182 AN: 1040238

Other (OTH) AF: 0.00823 AC: 444 AN: 53932

GnomAD4 genome AF: 0.0418 AC: 6371 AN: 152360 Hom.: 462 Cov.: 33 AF XY: 0.0395 AC XY: 2941 AN XY: 74506

African (AFR) AF: 0.146 AC: 6079 AN: 41584

American (AMR) AF: 0.0134 AC: 205 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68038

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0462 Hom.: 244

Bravo AF: 0.0461

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		0.26
PromoterAI		-0.083	Neutral
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: rs1018784; hg19: chr12-109536016;