4-69107326-A-T

Variant names:

• chr4-69107326-A-T
• rs4337789
• NM_001074.4:c.1090+64A>T

Variant summary

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

The NM_001074.4(UGT2B7):​c.1090+64A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,456,138 control chromosomes in the GnomAD database, including 191,054 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 (27884 hom., cov: 32)
  • Exomes 𝑓: 0.49 (163170 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.496
• Publications: 3 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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 rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1090+64A>T		intron_variant	Intron 4 of 5	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1090+64A>T		intron_variant	Intron 4 of 4		NP_001317648.1
UGT2B7	NM_001349568.2	c.343+64A>T		intron_variant	Intron 5 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1090+64A>T		intron_variant	Intron 4 of 5	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89673 AN: 151864 Hom.: 27835 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.493 AC: 643387 AN: 1304156 Hom.: 163170 AF XY: 0.493 AC XY: 321599 AN XY: 651790

African (AFR) AF: 0.776 AC: 21304 AN: 27448

American (AMR) AF: 0.705 AC: 19483 AN: 27648

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 11503 AN: 22422

East Asian (EAS) AF: 0.707 AC: 26204 AN: 37048

South Asian (SAS) AF: 0.521 AC: 37540 AN: 72094

European-Finnish (FIN) AF: 0.583 AC: 29571 AN: 50684

Middle Eastern (MID) AF: 0.532 AC: 2686 AN: 5046

European-Non Finnish (NFE) AF: 0.463 AC: 467103 AN: 1007840

Other (OTH) AF: 0.519 AC: 27993 AN: 53926

GnomAD4 genome AF: 0.591 AC: 89778 AN: 151982 Hom.: 27884 Cov.: 32 AF XY: 0.598 AC XY: 44433 AN XY: 74282

African (AFR) AF: 0.766 AC: 31786 AN: 41482

American (AMR) AF: 0.665 AC: 10156 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1774 AN: 3468

East Asian (EAS) AF: 0.700 AC: 3607 AN: 5150

South Asian (SAS) AF: 0.554 AC: 2674 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6045 AN: 10526

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.469 AC: 31852 AN: 67946

Other (OTH) AF: 0.599 AC: 1268 AN: 2116

Alfa AF: 0.379 Hom.: 1018

Bravo AF: 0.607

Asia WGS AF: 0.637 AC: 2209 AN: 3472

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	-0.94
CADD	Benign	0.55
DANN	Benign	0.36
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs4337789; hg19: chr4-69973044; COSMIC: COSV59443122;