rs73823859

Variant names:

• chr4-69096383-G-A
• rs73823859
• NM_001349568.2:c.-26-2157G>A

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-2157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,366,818 control chromosomes in the GnomAD database, including 758 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 (119 hom., cov: 33)
  • Exomes 𝑓: 0.026 (639 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.38
• Publications: 10 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=-0.86).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0996 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.-26-2157G>A		intron	N/A	NP_001336497.1
	UGT2B7	NM_001074.4	MANE Select	c.-138G>A		upstream_gene	N/A	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.-138G>A		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.-26-2157G>A		intron	N/A	ENSP00000426206.1	D6RH08
	UGT2B7	ENST00000509763.1	TSL:5	n.260-2157G>A		intron	N/A
	ENSG00000299782	ENST00000766360.1		n.443-894C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5084 AN: 152108 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0259 AC: 31410 AN: 1214592 Hom.: 639 AF XY: 0.0257 AC XY: 15558 AN XY: 605058

African (AFR) AF: 0.0487 AC: 1315 AN: 27012

American (AMR) AF: 0.0238 AC: 613 AN: 25806

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 2491 AN: 19708

East Asian (EAS) AF: 0.0000537 AC: 2 AN: 37270

South Asian (SAS) AF: 0.0102 AC: 683 AN: 67202

European-Finnish (FIN) AF: 0.0283 AC: 1296 AN: 45752

Middle Eastern (MID) AF: 0.107 AC: 547 AN: 5112

European-Non Finnish (NFE) AF: 0.0241 AC: 22579 AN: 935192

Other (OTH) AF: 0.0366 AC: 1884 AN: 51538

GnomAD4 genome AF: 0.0333 AC: 5076 AN: 152226 Hom.: 119 Cov.: 33 AF XY: 0.0332 AC XY: 2468 AN XY: 74434

African (AFR) AF: 0.0420 AC: 1746 AN: 41554

American (AMR) AF: 0.0331 AC: 506 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4828

European-Finnish (FIN) AF: 0.0321 AC: 340 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0271 AC: 1841 AN: 67990

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0296 Hom.: 110

Bravo AF: 0.0355

Asia WGS AF: 0.00866 AC: 30 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	-0.86
CADD	Benign	0.16
DANN	Benign	0.26
PhyloP100		-1.4
PromoterAI		-0.037	Neutral

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: rs73823859; hg19: chr4-69962101;