4-69645709-G-C

Position:

• chr4-69645709-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252275.3(UGT2A1):​c.715+1221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 151,628 control chromosomes in the GnomAD database, including 51,164 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51164 hom., cov: 32)
• Consequence: UGT2A1 NM_001252275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2A1	NM_001252275.3	c.715+1221C>G		intron_variant		ENST00000286604.9	NP_001239204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2A1	ENST00000286604.9	c.715+1221C>G		intron_variant		1	NM_001252275.3	ENSP00000286604.4
UGT2A1	ENST00000503640.5	c.715+1221C>G		intron_variant		1		ENSP00000424478.1
UGT2A1	ENST00000512704.5	c.715+1221C>G		intron_variant		1		ENSP00000421432.1
UGT2A1	ENST00000514019.1	c.715+1221C>G		intron_variant		2		ENSP00000425497.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124145 AN: 151510 Hom.: 51136 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.814

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124229 AN: 151628 Hom.: 51164 Cov.: 32 AF XY: 0.816 AC XY: 60490 AN XY: 74088

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.810

Alfa AF: 0.806 Hom.: 5868

Bravo AF: 0.831

Asia WGS AF: 0.824 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1560605; hg19: chr4-70511427;