4-69588571-A-G

Variant names:

• chr4-69588571-A-G
• rs4148312
• NM_001105677.2:c.*801T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.*801T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.*801T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000286604.9	NP_001239204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2A2	ENST00000604629.6	c.*801T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.*801T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001252275.3	ENSP00000286604.4
UGT2A1	ENST00000503640.5	c.*801T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000424478.1
UGT2A1	ENST00000512704.5	c.*801T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000421432.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.610 AC: 25295 AN: 41452

American (AMR) AF: 0.662 AC: 10091 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2503 AN: 3472

East Asian (EAS) AF: 0.741 AC: 3819 AN: 5152

South Asian (SAS) AF: 0.712 AC: 3425 AN: 4808

European-Finnish (FIN) AF: 0.547 AC: 5746 AN: 10496

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.595 AC: 40412 AN: 67888

Other (OTH) AF: 0.641 AC: 1352 AN: 2110

Alfa AF: 0.608 Hom.: 3635

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
PhyloP100		-0.74
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: rs4148312; hg19: chr4-70454289;