4-69098803-G-A

Position:

• chr4-69098803-G-A

Variant summary

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

The ENST00000305231.12(UGT2B7):​c.870+115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,532,098 control chromosomes in the GnomAD database, including 196,687 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 0.58 (26290 hom., cov: 32)
  • Exomes 𝑓: 0.49 (170397 hom.)
• Consequence: UGT2B7 ENST00000305231.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.870+115G>A		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.870+115G>A		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.123+115G>A		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.870+115G>A		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87528 AN: 151666 Hom.: 26244 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.490 AC: 676963 AN: 1380314 Hom.: 170397 AF XY: 0.492 AC XY: 337457 AN XY: 686172

Gnomad4 AFR exome AF: 0.717

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.577 AC: 87629 AN: 151784 Hom.: 26290 Cov.: 32 AF XY: 0.586 AC XY: 43477 AN XY: 74162

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.588

Alfa AF: 0.374 Hom.: 990

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0060
DANN	Benign	0.74

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: rs7441750; hg19: chr4-69964521;