rs3924194

Positions:

• chr4-69105374-C-G

Variant summary

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

The NM_001074.4(UGT2B7):​c.1003-1801C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,232 control chromosomes in the GnomAD database, including 943 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 0.092 (943 hom., cov: 33)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.1003-1801C>G		intron_variant		ENST00000305231.12
UGT2B7	NM_001330719.2	c.1003-1801C>G		intron_variant
UGT2B7	NM_001349568.2	c.256-1801C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1003-1801C>G		intron_variant		1	NM_001074.4	P1

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14025 AN: 152114 Hom.: 943 Cov.: 33

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0921 AC: 14021 AN: 152232 Hom.: 943 Cov.: 33 AF XY: 0.0892 AC XY: 6639 AN XY: 74436

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0561

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.123 Hom.: 183

Bravo AF: 0.0818

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.016
DANN	Benign	0.39

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: rs3924194; hg19: chr4-69971092;