rs4521414

Positions:

• chr4-69107807-C-A
• chr4-69107807-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.1091-296C>A 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 151,742 control chromosomes in the GnomAD database, including 27,834 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 (27834 hom., cov: 30)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.95).
• 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/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1091-296C>A		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1090+545C>A		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.344-296C>A		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1091-296C>A		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89509 AN: 151624 Hom.: 27785 Cov.: 30

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.591 AC: 89614 AN: 151742 Hom.: 27834 Cov.: 30 AF XY: 0.598 AC XY: 44362 AN XY: 74148

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.600

Alfa AF: 0.499 Hom.: 18610

Bravo AF: 0.607

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.21

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: rs4521414; hg19: chr4-69973525;