4-69485380-T-C

Position:

• chr4-69485380-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021139.3(UGT2B4):​c.1138A>G​(p.Ile380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B4 NM_021139.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.205

Genes affected

UGT2B4 (HGNC:12553): (UDP glucuronosyltransferase family 2 member B4) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation and estrogen metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1319286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B4	NM_021139.3	c.1138A>G	p.Ile380Val	missense_variant	5/6	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2	c.730A>G	p.Ile244Val	missense_variant	6/7		NP_001284545.1
UGT2B4	NM_001297615.2	c.1090+1229A>G		intron_variant			NP_001284544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7	c.1138A>G	p.Ile380Val	missense_variant	5/6	1	NM_021139.3	ENSP00000305221	P1
UGT2B4	ENST00000512583.5	c.1090+1229A>G		intron_variant		1		ENSP00000421290
UGT2B4	ENST00000502655.5	n.1015A>G		non_coding_transcript_exon_variant	6/6	5
UGT2B4	ENST00000506580.5	n.872+1229A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2021

The c.1138A>G (p.I380V) alteration is located in exon 5 (coding exon 5) of the UGT2B4 gene. This alteration results from a A to G substitution at nucleotide position 1138, causing the isoleucine (I) at amino acid position 380 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.44
DANN	Benign	0.44
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.028
Sift	Benign	0.17	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.58		Gain of phosphorylation at Y381 (P = 0.1219);
MVP		0.072
MPC		0.012
ClinPred		0.76	D
GERP RS		-2.6
Varity_R		0.070
gMVP		0.099

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: chr4-70351098;