chr4-69098462-T-C

Variant names:

• chr4-69098462-T-C
• rs7439326
• NM_001074.4:c.722-78T>C

Variant summary

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

The NM_001074.4(UGT2B7):​c.722-78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,524,446 control chromosomes in the GnomAD database, including 193,218 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 0.58 (26190 hom., cov: 31)
  • Exomes 𝑓: 0.49 (167028 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.382
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. 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.722-78T>C		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.722-78T>C		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.-26-78T>C		intron	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.722-78T>C		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.722-78T>C		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.722-78T>C		intron	N/A	ENSP00000483172.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87249 AN: 151346 Hom.: 26144 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.487 AC: 667958 AN: 1372982 Hom.: 167028 AF XY: 0.488 AC XY: 331909 AN XY: 680806

African (AFR) AF: 0.712 AC: 20783 AN: 29208

American (AMR) AF: 0.684 AC: 19066 AN: 27866

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 11452 AN: 22670

East Asian (EAS) AF: 0.700 AC: 26664 AN: 38070

South Asian (SAS) AF: 0.558 AC: 40417 AN: 72472

European-Finnish (FIN) AF: 0.575 AC: 29153 AN: 50672

Middle Eastern (MID) AF: 0.524 AC: 2833 AN: 5402

European-Non Finnish (NFE) AF: 0.457 AC: 488699 AN: 1070118

Other (OTH) AF: 0.511 AC: 28891 AN: 56504

GnomAD4 genome AF: 0.577 AC: 87350 AN: 151464 Hom.: 26190 Cov.: 31 AF XY: 0.585 AC XY: 43310 AN XY: 73976

African (AFR) AF: 0.713 AC: 29492 AN: 41384

American (AMR) AF: 0.659 AC: 9990 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3464

East Asian (EAS) AF: 0.702 AC: 3614 AN: 5150

South Asian (SAS) AF: 0.604 AC: 2912 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 5953 AN: 10404

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

European-Non Finnish (NFE) AF: 0.469 AC: 31763 AN: 67780

Other (OTH) AF: 0.588 AC: 1239 AN: 2106

Alfa AF: 0.517 Hom.: 4347

Bravo AF: 0.590

Asia WGS AF: 0.655 AC: 2274 AN: 3476

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	-0.83
CADD	Benign	3.7
DANN	Benign	0.84
PhyloP100		-0.38
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: rs7439326; hg19: chr4-69964180; COSMIC: COSV59441814;