4-69098553-A-G

Variant names:

• chr4-69098553-A-G
• rs28365062
• NM_001074.4:c.735A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001074.4(UGT2B7):​c.735A>G​(p.Thr245Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,604,518 control chromosomes in the GnomAD database, including 18,331 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 0.16 (2152 hom., cov: 30)
  • Exomes 𝑓: 0.14 (16179 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.276
• Publications: 43 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.276 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.735A>G	p.Thr245Thr	synonymous_variant	Exon 2 of 6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.735A>G	p.Thr245Thr	synonymous_variant	Exon 2 of 5		NP_001317648.1
UGT2B7	NM_001349568.2	c.-13A>G		5_prime_UTR_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.735A>G	p.Thr245Thr	synonymous_variant	Exon 2 of 6	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.159 AC: 23917 AN: 150748 Hom.: 2149 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.172 AC: 42073 AN: 244836 AF XY: 0.162

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0437

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.138 AC: 200354 AN: 1453658 Hom.: 16179 Cov.: 43 AF XY: 0.136 AC XY: 98393 AN XY: 723090

African (AFR) AF: 0.146 AC: 4784 AN: 32790

American (AMR) AF: 0.371 AC: 15727 AN: 42360

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3758 AN: 25970

East Asian (EAS) AF: 0.0609 AC: 2408 AN: 39566

South Asian (SAS) AF: 0.122 AC: 10297 AN: 84466

European-Finnish (FIN) AF: 0.245 AC: 13075 AN: 53320

Middle Eastern (MID) AF: 0.150 AC: 864 AN: 5744

European-Non Finnish (NFE) AF: 0.127 AC: 141179 AN: 1109354

Other (OTH) AF: 0.137 AC: 8262 AN: 60088

GnomAD4 genome AF: 0.159 AC: 23936 AN: 150860 Hom.: 2152 Cov.: 30 AF XY: 0.165 AC XY: 12137 AN XY: 73594

African (AFR) AF: 0.151 AC: 6208 AN: 41044

American (AMR) AF: 0.275 AC: 4163 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 490 AN: 3462

East Asian (EAS) AF: 0.0476 AC: 244 AN: 5128

South Asian (SAS) AF: 0.123 AC: 586 AN: 4774

European-Finnish (FIN) AF: 0.244 AC: 2520 AN: 10308

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9156 AN: 67732

Other (OTH) AF: 0.178 AC: 373 AN: 2092

Alfa AF: 0.124 Hom.: 785

Bravo AF: 0.164

Asia WGS AF: 0.115 AC: 399 AN: 3478

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	-0.86
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs28365062; hg19: chr4-69964271; COSMIC: COSV59443088;