rs34661811

Variant names:

• chr4-69098673-C-A
• rs34661811
• NM_001074.4:c.855C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-69098673-C-A
• chr4-69098673-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001074.4(UGT2B7):​c.855C>A​(p.Ala285Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,610,488 control chromosomes in the GnomAD database, including 907 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 0.033 (116 hom., cov: 32)
  • Exomes 𝑓: 0.026 (791 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.297
• Publications: 6 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-0.297 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.855C>A	p.Ala285Ala	synonymous_variant	Exon 2 of 6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.855C>A	p.Ala285Ala	synonymous_variant	Exon 2 of 5		NP_001317648.1
UGT2B7	NM_001349568.2	c.108C>A	p.Ala36Ala	synonymous_variant	Exon 3 of 7		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.855C>A	p.Ala285Ala	synonymous_variant	Exon 2 of 6	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5064 AN: 151884 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0479

GnomAD2 exomes AF: 0.0288 AC: 7139 AN: 248162 AF XY: 0.0285

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0290

Gnomad OTH exome AF: 0.0403

GnomAD4 exome AF: 0.0262 AC: 38279 AN: 1458486 Hom.: 791 Cov.: 33 AF XY: 0.0260 AC XY: 18885 AN XY: 725626

African (AFR) AF: 0.0478 AC: 1584 AN: 33166

American (AMR) AF: 0.0220 AC: 965 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3324 AN: 26038

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39626

South Asian (SAS) AF: 0.0103 AC: 885 AN: 85872

European-Finnish (FIN) AF: 0.0282 AC: 1508 AN: 53394

Middle Eastern (MID) AF: 0.106 AC: 611 AN: 5760

European-Non Finnish (NFE) AF: 0.0245 AC: 27204 AN: 1110540

Other (OTH) AF: 0.0364 AC: 2196 AN: 60260

GnomAD4 genome AF: 0.0333 AC: 5056 AN: 152002 Hom.: 116 Cov.: 32 AF XY: 0.0331 AC XY: 2457 AN XY: 74296

African (AFR) AF: 0.0419 AC: 1740 AN: 41518

American (AMR) AF: 0.0330 AC: 503 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 473 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4824

European-Finnish (FIN) AF: 0.0319 AC: 338 AN: 10590

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1830 AN: 67896

Other (OTH) AF: 0.0474 AC: 100 AN: 2108

Alfa AF: 0.0376 Hom.: 74

Bravo AF: 0.0354

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0330

EpiControl AF: 0.0376

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	-0.38
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34661811; hg19: chr4-69964391;