chr4-69635828-C-CAAAAAAAAAAAAAAAAAAA

Variant names:

• chr4-69635828-C-CAAAAAAAAAAAAAAAAAAA
• rs1191267919
• NM_001105677.2:c.742+3052_742+3070dupTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001252275.3(UGT2A1):​c.716-25_716-7dupTTTTTTTTTTTTTTTTTTT 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 0.012 (222 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

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0124 (609/49084) while in subpopulation EAS AF= 0.0302 (44/1456). AF 95% confidence interval is 0.0231. There are 222 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 222 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.742+3052_742+3070dupTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 1 of 5	ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.716-25_716-7dupTTTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 2 of 6	ENST00000286604.9	NP_001239204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2A2	ENST00000604629.6	c.742+3070_742+3071insTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 1 of 5	1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.716-7_716-6insTTTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 2 of 6	1	NM_001252275.3	ENSP00000286604.4

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 609 AN: 49076 Hom.: 222 Cov.: 0

Gnomad AFR AF: 0.00762

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00803

Gnomad MID AF: 0.0652

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0120

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

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.0124 AC: 609 AN: 49084 Hom.: 222 Cov.: 0 AF XY: 0.0118 AC XY: 257 AN XY: 21710

Gnomad4 AFR AF: 0.00762

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0302

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.00803

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1191267919; hg19: chr4-70501546;