4-69096569-TG-T

Variant names:

• chr4-69096569-TG-T
• rs1577920742
• NM_001074.4:c.50delG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001074.4(UGT2B7):​c.50delG​(p.Cys17SerfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B7 NM_001074.4 frameshift
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.314
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001074.4	MANE Select	c.50delG	p.Cys17SerfsTer21	frameshift	Exon 1 of 6	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.50delG	p.Cys17SerfsTer21	frameshift	Exon 1 of 5	NP_001317648.1	E9PBP8
	UGT2B7	NM_001349568.2		c.-26-1970delG		intron	N/A	NP_001336497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.50delG	p.Cys17SerfsTer21	frameshift	Exon 1 of 6	ENSP00000304811.7	P16662
	UGT2B7	ENST00000868341.1		c.50delG	p.Cys17SerfsTer21	frameshift	Exon 1 of 7	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.50delG	p.Cys17SerfsTer21	frameshift	Exon 1 of 7	ENSP00000538402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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
PhyloP100		-0.31

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: rs1577920742; hg19: chr4-69962287;