chr4-69635828-C-CAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• 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: Likely_benign. The variant received -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 VariationId is 3771717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 101 AR gene

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

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

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

African (AFR) AF: 0.00364 AC: 55 AN: 15124

American (AMR) AF: 0.00740 AC: 23 AN: 3110

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 5 AN: 1306

East Asian (EAS) AF: 0.0185 AC: 27 AN: 1456

South Asian (SAS) AF: 0.00253 AC: 2 AN: 792

European-Finnish (FIN) AF: 0.00803 AC: 7 AN: 872

Middle Eastern (MID) AF: 0.0217 AC: 1 AN: 46

European-Non Finnish (NFE) AF: 0.00589 AC: 150 AN: 25474

Other (OTH) AF: 0.00 AC: 0 AN: 586

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

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;