4-69635828-CA-CAAAAAAAAAAAAA

Variant names:

• chr4-69635828-C-CAAAAAAAAAAAA
• rs1191267919
• NM_001105677.2:c.742+3059_742+3070dupTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001252275.3(UGT2A1):​c.716-18_716-7dupTTTTTTTTTTTT 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 0.00094 (10 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.742+3059_742+3070dupTTTTTTTTTTTT		intron_variant	Intron 1 of 5	ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.716-18_716-7dupTTTTTTTTTTTT		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+3071insTTTTTTTTTTTT		intron_variant	Intron 1 of 5	1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.716-7_716-6insTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 2 of 6	1	NM_001252275.3	ENSP00000286604.4

Frequencies

GnomAD3 genomes AF: 0.000937 AC: 46 AN: 49112 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.000860

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00128

Gnomad ASJ AF: 0.000766

Gnomad EAS AF: 0.00206

Gnomad SAS AF: 0.00254

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000864

Gnomad OTH AF: 0.00

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: 0.000936 AC: 46 AN: 49120 Hom.: 10 Cov.: 0 AF XY: 0.000691 AC XY: 15 AN XY: 21722

Gnomad4 AFR AF: 0.000859

Gnomad4 AMR AF: 0.00129

Gnomad4 ASJ AF: 0.000766

Gnomad4 EAS AF: 0.00206

Gnomad4 SAS AF: 0.00253

Gnomad4 FIN AF: 0.00115

Gnomad4 NFE AF: 0.000864

Gnomad4 OTH AF: 0.00

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;