4-69598136-T-A

Position:

• chr4-69598136-T-A

Variant summary

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

The NM_001105677.2(UGT2A2):​c.891+1110A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,072 control chromosomes in the GnomAD database, including 4,964 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 0.25 (4964 hom., cov: 32)
• Consequence: UGT2A2 NM_001105677.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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]

UGT2A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.891+1110A>T		intron_variant		ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.996+1110A>T		intron_variant		ENST00000286604.9	NP_001239204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2A2	ENST00000604629.6	c.891+1110A>T		intron_variant		1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.996+1110A>T		intron_variant		1	NM_001252275.3	ENSP00000286604.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37394 AN: 151954 Hom.: 4967 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.246 AC: 37396 AN: 152072 Hom.: 4964 Cov.: 32 AF XY: 0.245 AC XY: 18189 AN XY: 74354

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.282

Alfa AF: 0.223 Hom.: 561

Bravo AF: 0.252

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.56

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: rs3775783; hg19: chr4-70463854;