4-69635828-CA-CAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr4-69635828-C-CAAAAAAAAAAAAAAAAAAAAAAA
• rs1191267919
• NM_001105677.2:c.742+3070_742+3071insTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001252275.3(UGT2A1):​c.716-7_716-6insTTTTTTTTTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (101 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2A1 NM_001252275.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP6: Variant 4-69635828-C-CAAAAAAAAAAAAAAAAAAAAAAA is Benign according to our data. Variant chr4-69635828-C-CAAAAAAAAAAAAAAAAAAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 3771717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 272 AN: 49110 Hom.: 101 Cov.: 0

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00568

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00383

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00254

Gnomad FIN AF: 0.00803

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.00589

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: 0.00554 AC: 272 AN: 49118 Hom.: 101 Cov.: 0 AF XY: 0.00557 AC XY: 121 AN XY: 21718

Gnomad4 AFR AF: 0.00364

Gnomad4 AMR AF: 0.00740

Gnomad4 ASJ AF: 0.00383

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.00253

Gnomad4 FIN AF: 0.00803

Gnomad4 NFE AF: 0.00589

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UGT2A1: BP4, BS2 -

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;