4-69635828-CA-CAAAA

Variant names:

• chr4-69635828-C-CAAA
• rs1191267919
• NM_001105677.2:c.742+3068_742+3070dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001252275.3(UGT2A1):​c.716-9_716-7dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (642 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

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+3068_742+3070dupTTT		intron	N/A	NP_001099147.2	P0DTE5-1
	UGT2A1	NM_001252275.3	MANE Select	c.716-9_716-7dupTTT		splice_region intron	N/A	NP_001239204.2	P0DTE4-5
	UGT2A1	NM_001389565.1		c.1345+3068_1345+3070dupTTT		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+3071insTTT		intron	N/A	ENSP00000475028.2	P0DTE5-1
	UGT2A1	ENST00000286604.9	TSL:1 MANE Select	c.716-7_716-6insTTT		splice_region intron	N/A	ENSP00000286604.4	P0DTE4-5
	UGT2A1	ENST00000503640.5	TSL:1	c.715+11101_715+11102insTTT		intron	N/A	ENSP00000424478.1	P0DTE4-1

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 4008 AN: 49130 Hom.: 642 Cov.: 0

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0859

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: 0.0815 AC: 4007 AN: 49138 Hom.: 642 Cov.: 0 AF XY: 0.0752 AC XY: 1633 AN XY: 21720

African (AFR) AF: 0.0386 AC: 581 AN: 15042

American (AMR) AF: 0.0483 AC: 150 AN: 3104

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 131 AN: 1322

East Asian (EAS) AF: 0.0371 AC: 54 AN: 1454

South Asian (SAS) AF: 0.0392 AC: 31 AN: 790

European-Finnish (FIN) AF: 0.0389 AC: 34 AN: 874

Middle Eastern (MID) AF: 0.0625 AC: 3 AN: 48

European-Non Finnish (NFE) AF: 0.112 AC: 2859 AN: 25564

Other (OTH) AF: 0.0856 AC: 50 AN: 584

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;