chr4-69635828-C-CAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.742+3068_742+3070dupTTT		intron_variant	Intron 1 of 5	ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.716-9_716-7dupTTT		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+3071insTTT		intron_variant	Intron 1 of 5	1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.716-7_716-6insTTT		splice_region_variant, intron_variant	Intron 2 of 6	1	NM_001252275.3	ENSP00000286604.4

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

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.0815 AC: 4007 AN: 49138 Hom.: 642 Cov.: 0 AF XY: 0.0752 AC XY: 1633 AN XY: 21720

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0856

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;