4-69096194-A-G

Variant names:

• chr4-69096194-A-G
• rs7662029
• NM_001349568.2:c.-26-2346A>G

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-2346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,992 control chromosomes in the GnomAD database, including 26,306 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 (26306 hom., cov: 33)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 58 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:58802):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349568.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001349568.2		c.-26-2346A>G		intron	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000502942.5	TSL:2	c.-26-2346A>G		intron	N/A	ENSP00000426206.1
	UGT2B7	ENST00000509763.1	TSL:5	n.260-2346A>G		intron	N/A
	ENSG00000299782	ENST00000766360.1		n.443-705T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87598 AN: 151874 Hom.: 26260 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.577 AC: 87699 AN: 151992 Hom.: 26306 Cov.: 33 AF XY: 0.586 AC XY: 43510 AN XY: 74284

African (AFR) AF: 0.713 AC: 29556 AN: 41462

American (AMR) AF: 0.660 AC: 10067 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3627 AN: 5168

South Asian (SAS) AF: 0.604 AC: 2911 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6068 AN: 10578

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

European-Non Finnish (NFE) AF: 0.469 AC: 31834 AN: 67922

Other (OTH) AF: 0.589 AC: 1242 AN: 2108

Alfa AF: 0.513 Hom.: 66674

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.42
PhyloP100		-1.4
PromoterAI		0.023	Neutral

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

Other links and lift over

dbSNP: rs7662029; hg19: chr4-69961912;