NM_001074.4:c.130G>A

Variant names:

• chr4-69096650-G-A
• rs1577920819
• NM_001074.4:c.130G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001074.4(UGT2B7):​c.130G>A​(p.Asp44Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2B7 NM_001074.4 missense
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.702
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20724633).

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.130G>A	p.Asp44Asn	missense	Exon 1 of 6	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.130G>A	p.Asp44Asn	missense	Exon 1 of 5	NP_001317648.1	E9PBP8
	UGT2B7	NM_001349568.2		c.-26-1890G>A		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.130G>A	p.Asp44Asn	missense	Exon 1 of 6	ENSP00000304811.7	P16662
	UGT2B7	ENST00000868341.1		c.130G>A	p.Asp44Asn	missense	Exon 1 of 7	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.130G>A	p.Asp44Asn	missense	Exon 1 of 7	ENSP00000538402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60390

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
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.70
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.12
Sift	Benign	0.069	T
Sift4G	Uncertain	0.042	D
Polyphen		0.0050	B
Vest4		0.046
MutPred		0.51		Gain of ubiquitination at K40 (P = 0.2995)
MVP		0.11
MPC		0.029
ClinPred		0.51	D
GERP RS		1.7
PromoterAI		-0.014	Neutral
Varity_R		0.11
gMVP		0.093
Mutation Taster		=93/7	polymorphism

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: rs1577920819; hg19: chr4-69962368;