rs762365097

Variant names:

• chr4-69096347-C-A
• rs762365097
• NM_001349568.2:c.-26-2193C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-69096347-C-A
• chr4-69096347-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349568.2(UGT2B7):​c.-26-2193C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 837,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -3.02
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.-26-2193C>A		intron	N/A	NP_001336497.1
	UGT2B7	NM_001074.4	MANE Select	c.-174C>A		upstream_gene	N/A	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.-174C>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.-26-2193C>A		intron	N/A	ENSP00000426206.1	D6RH08
	UGT2B7	ENST00000509763.1	TSL:5	n.260-2193C>A		intron	N/A
	ENSG00000299782	ENST00000766360.1		n.443-858G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 837870 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 425512

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19206

American (AMR) AF: 0.00 AC: 0 AN: 19558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16062

East Asian (EAS) AF: 0.00 AC: 0 AN: 32836

South Asian (SAS) AF: 0.00 AC: 0 AN: 54902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4154

European-Non Finnish (NFE) AF: 0.00000162 AC: 1 AN: 617178

Other (OTH) AF: 0.00 AC: 0 AN: 38736

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

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	-0.82
CADD	Benign	0.042
DANN	Benign	0.55
PhyloP100		-3.0
PromoterAI		-0.011	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: rs762365097; hg19: chr4-69962065;