4-69635828-CA-CAAAAAAAAAAAAAAAAAAA

Variant names:

• chr4-69635828-C-CAAAAAAAAAAAAAAAAAA
• rs1191267919
• NM_001105677.2:c.742+3053_742+3070dupTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001252275.3(UGT2A1):​c.716-24_716-7dupTTTTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (306 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2A1 NM_001252275.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0185 (910/49072) while in subpopulation EAS AF = 0.0419 (61/1456). AF 95% confidence interval is 0.0335. There are 306 homozygotes in GnomAd4. There are 434 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 306 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	NM_001105677.2	MANE Select	c.742+3053_742+3070dupTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001099147.2	P0DTE5-1
	UGT2A1	NM_001252275.3	MANE Select	c.716-24_716-7dupTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_001239204.2	P0DTE4-5
	UGT2A1	NM_001389565.1		c.1345+3053_1345+3070dupTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001376494.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	ENST00000604629.6	TSL:1 MANE Select	c.742+3070_742+3071insTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000475028.2	P0DTE5-1
	UGT2A1	ENST00000286604.9	TSL:1 MANE Select	c.716-7_716-6insTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000286604.4	P0DTE4-5
	UGT2A1	ENST00000503640.5	TSL:1	c.715+11101_715+11102insTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000424478.1	P0DTE4-1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 910 AN: 49064 Hom.: 306 Cov.: 0

Gnomad AFR AF: 0.00822

Gnomad AMI AF: 0.00852

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0229

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0103

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AF: 0.00 AC: 0 AN: 2

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: 0.0185 AC: 910 AN: 49072 Hom.: 306 Cov.: 0 AF XY: 0.0200 AC XY: 434 AN XY: 21702

African (AFR) AF: 0.00822 AC: 124 AN: 15086

American (AMR) AF: 0.0299 AC: 93 AN: 3108

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 24 AN: 1306

East Asian (EAS) AF: 0.0419 AC: 61 AN: 1456

South Asian (SAS) AF: 0.0227 AC: 18 AN: 792

European-Finnish (FIN) AF: 0.0172 AC: 15 AN: 870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 46

European-Non Finnish (NFE) AF: 0.0222 AC: 566 AN: 25470

Other (OTH) AF: 0.0102 AC: 6 AN: 586

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1191267919; hg19: chr4-70501546;