chr4-69096360-T-C

Variant names:

• chr4-69096360-T-C
• rs7668258
• NM_001349568.2:c.-26-2180T>C

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-2180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,130,256 control chromosomes in the GnomAD database, including 149,632 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 (26313 hom., cov: 32)
  • Exomes 𝑓: 0.49 (123319 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.67
• Publications: 95 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=-0.88).
• 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_001349568.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001349568.2		c.-26-2180T>C		intron	N/A	NP_001336497.1
	UGT2B7	NM_001074.4	MANE Select	c.-161T>C		upstream_gene	N/A	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.-161T>C		upstream_gene	N/A	NP_001317648.1	E9PBP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000502942.5	TSL:2	c.-26-2180T>C		intron	N/A	ENSP00000426206.1	D6RH08
	UGT2B7	ENST00000509763.1	TSL:5	n.260-2180T>C		intron	N/A
	ENSG00000299782	ENST00000766360.1		n.443-871A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87599 AN: 151876 Hom.: 26267 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.494 AC: 483291 AN: 978262 Hom.: 123319 AF XY: 0.496 AC XY: 243703 AN XY: 491698

African (AFR) AF: 0.714 AC: 15779 AN: 22106

American (AMR) AF: 0.683 AC: 14150 AN: 20730

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 8779 AN: 17224

East Asian (EAS) AF: 0.704 AC: 24159 AN: 34318

South Asian (SAS) AF: 0.569 AC: 33602 AN: 59034

European-Finnish (FIN) AF: 0.578 AC: 22364 AN: 38718

Middle Eastern (MID) AF: 0.531 AC: 2414 AN: 4542

European-Non Finnish (NFE) AF: 0.460 AC: 339486 AN: 738108

Other (OTH) AF: 0.519 AC: 22558 AN: 43482

GnomAD4 genome AF: 0.577 AC: 87700 AN: 151994 Hom.: 26313 Cov.: 32 AF XY: 0.586 AC XY: 43528 AN XY: 74296

African (AFR) AF: 0.713 AC: 29570 AN: 41482

American (AMR) AF: 0.660 AC: 10060 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3470

East Asian (EAS) AF: 0.702 AC: 3624 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2913 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6067 AN: 10562

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31828 AN: 67926

Other (OTH) AF: 0.588 AC: 1244 AN: 2114

Alfa AF: 0.517 Hom.: 59733

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.60
PhyloP100		-1.7
PromoterAI		-0.0070	Neutral
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: rs7668258; hg19: chr4-69962078; COSMIC: COSV59441822;