4-69113032-T-C

Variant names:

• chr4-69113032-T-C
• rs6851533
• NM_001074.4:c.*296T>C

Variant summary

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

The NM_001074.4(UGT2B7):​c.*296T>C variant causes a downstream gene 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: UGT2B7 NM_001074.4 downstream_gene
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.273

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.*296T>C		downstream_gene_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.*556T>C		downstream_gene_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.*296T>C		downstream_gene_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.*296T>C		downstream_gene_variant		1	NM_001074.4	ENSP00000304811.7
UGT2B7	ENST00000508661.5	c.*556T>C		downstream_gene_variant		2		ENSP00000427659.1
UGT2B7	ENST00000622664.1	c.*570T>C		downstream_gene_variant		5		ENSP00000483172.1

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

Gnomad4 AFR exome AF: 0.723

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.499

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

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.600

Alfa AF: 0.525 Hom.: 3532

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.70

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: rs6851533; hg19: chr4-69978750;