chr4-69096650-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001074.4(UGT2B7):​c.130G>T​(p.Asp44Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UGT2B7 NM_001074.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27078614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.130G>T	p.Asp44Tyr	missense_variant	Exon 1 of 6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.130G>T	p.Asp44Tyr	missense_variant	Exon 1 of 5		NP_001317648.1
UGT2B7	NM_001349568.2	c.-26-1890G>T		intron_variant	Intron 2 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.130G>T	p.Asp44Tyr	missense_variant	Exon 1 of 6	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.60
DEOGEN2	Uncertain	0.53	D;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.94
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.8	D;D;.
REVEL	Benign	0.19
Sift	Uncertain	0.023	D;D;.
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.012	B;B;.
Vest4		0.30
MutPred		0.54		Gain of ubiquitination at K40 (P = 0.1283);Gain of ubiquitination at K40 (P = 0.1283);Gain of ubiquitination at K40 (P = 0.1283);
MVP		0.14
MPC		0.032
ClinPred		0.58	D
GERP RS		1.7
Varity_R		0.31
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69962368;