NM_001074.4:c.1091-181A>G

Variant names:

• chr4-69107922-A-G
• rs4314345
• NM_001074.4:c.1091-181A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001074.4(UGT2B7):​c.1091-181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,030 control chromosomes in the GnomAD database, including 27,908 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 0.59 (27908 hom., cov: 32)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.956
• Publications: 1 publications found

Genes affected

UGT2B7 (HGNC:12554): (UDP glucuronosyltransferase family 2 member B7) The protein encoded by this gene belongs to the UDP-glycosyltransferase (UGT) family. UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This protein is localized in the microsome membrane, and has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ENSG00000299782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1091-181A>G		intron_variant	Intron 4 of 5	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1090+660A>G		intron_variant	Intron 4 of 4		NP_001317648.1
UGT2B7	NM_001349568.2	c.344-181A>G		intron_variant	Intron 5 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1091-181A>G		intron_variant	Intron 4 of 5	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89709 AN: 151914 Hom.: 27859 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.591 AC: 89814 AN: 152030 Hom.: 27908 Cov.: 32 AF XY: 0.598 AC XY: 44468 AN XY: 74304

African (AFR) AF: 0.766 AC: 31781 AN: 41478

American (AMR) AF: 0.665 AC: 10147 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1774 AN: 3468

East Asian (EAS) AF: 0.701 AC: 3621 AN: 5164

South Asian (SAS) AF: 0.555 AC: 2678 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6061 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31873 AN: 67972

Other (OTH) AF: 0.599 AC: 1261 AN: 2106

Alfa AF: 0.405 Hom.: 1242

Bravo AF: 0.607

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.59
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4314345; hg19: chr4-69973640;