4-69588571-A-G

Position:

• chr4-69588571-A-G

Variant summary

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

The NM_001105677.2(UGT2A2):​c.*801T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,826 control chromosomes in the GnomAD database, including 29,028 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 0.62 (29028 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: UGT2A2 NM_001105677.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

Genes affected

UGT2A2 (HGNC:28183): (UDP glucuronosyltransferase family 2 member A2) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A1 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

UGT2A1 (HGNC:12542): (UDP glucuronosyltransferase family 2 member A1 complex locus) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2A2	NM_001105677.2	c.*801T>C		3_prime_UTR_variant	6/6	ENST00000604629.6
UGT2A1	NM_001252275.3	c.*801T>C		3_prime_UTR_variant	7/7	ENST00000286604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A1	ENST00000286604.9	c.*801T>C		3_prime_UTR_variant	7/7	1	NM_001252275.3
UGT2A2	ENST00000604629.6	c.*801T>C		3_prime_UTR_variant	6/6	1	NM_001105677.2	P1
UGT2A1	ENST00000503640.5	c.*801T>C		3_prime_UTR_variant	6/6	1		P1
UGT2A1	ENST00000512704.5	c.*801T>C		3_prime_UTR_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93465 AN: 151706 Hom.: 29009 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.645

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.616 AC: 93536 AN: 151826 Hom.: 29028 Cov.: 32 AF XY: 0.616 AC XY: 45730 AN XY: 74186

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.641

Alfa AF: 0.608 Hom.: 3496

Bravo AF: 0.625

Asia WGS AF: 0.715 AC: 2458 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.58

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: rs4148312; hg19: chr4-70454289;