4-69113032-T-C

Variant names:

• chr4-69113032-T-C
• rs6851533
• ENST00000766360.1:n.253-328A>G

Variant summary

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

The ENST00000766360.1(ENSG00000299782):​n.253-328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 302,890 control chromosomes in the GnomAD database, including 46,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (27460 hom., cov: 31)
  • Exomes 𝑓: 0.49 (18807 hom.)
• Consequence: ENSG00000299782 ENST00000766360.1 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.273
• Publications: 6 publications found

Genes affected

ENSG00000299782 (HGNC:58802):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000766360.1. 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_001074.4	MANE Select	c.*296T>C		downstream_gene	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.*556T>C		downstream_gene	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.*296T>C		downstream_gene	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000299782	ENST00000766360.1		n.253-328A>G		intron	N/A
	ENSG00000299782	ENST00000766361.1		n.254-328A>G		intron	N/A
	ENSG00000299782	ENST00000766362.1		n.347-328A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89146 AN: 151740 Hom.: 27412 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.486 AC: 73437 AN: 151032 Hom.: 18807 Cov.: 4 AF XY: 0.487 AC XY: 38889 AN XY: 79854

African (AFR) AF: 0.723 AC: 1708 AN: 2364

American (AMR) AF: 0.673 AC: 3072 AN: 4568

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1759 AN: 3640

East Asian (EAS) AF: 0.694 AC: 3491 AN: 5032

South Asian (SAS) AF: 0.499 AC: 9986 AN: 20006

European-Finnish (FIN) AF: 0.564 AC: 3564 AN: 6316

Middle Eastern (MID) AF: 0.482 AC: 265 AN: 550

European-Non Finnish (NFE) AF: 0.453 AC: 45660 AN: 100684

Other (OTH) AF: 0.499 AC: 3932 AN: 7872

GnomAD4 genome AF: 0.588 AC: 89250 AN: 151858 Hom.: 27460 Cov.: 31 AF XY: 0.595 AC XY: 44170 AN XY: 74198

African (AFR) AF: 0.751 AC: 31103 AN: 41424

American (AMR) AF: 0.667 AC: 10177 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3632 AN: 5166

South Asian (SAS) AF: 0.550 AC: 2651 AN: 4822

European-Finnish (FIN) AF: 0.573 AC: 6019 AN: 10506

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

European-Non Finnish (NFE) AF: 0.471 AC: 32006 AN: 67890

Other (OTH) AF: 0.600 AC: 1269 AN: 2114

Alfa AF: 0.565 Hom.: 8111

Bravo AF: 0.603

Asia WGS AF: 0.633 AC: 2191 AN: 3466

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.70
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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: rs6851533; hg19: chr4-69978750;