NM_021139.3:c.1374T>A

Variant names:

• chr4-69480847-A-T
• rs13119049
• NM_021139.3:c.1374T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021139.3(UGT2B4):​c.1374T>A​(p.Asp458Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,560 control chromosomes in the GnomAD database, including 44,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.20 (3267 hom., cov: 31)
  • Exomes 𝑓: 0.23 (41399 hom.)
• Consequence: UGT2B4 NM_021139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009637177).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B4	NM_021139.3	MANE Select	c.1374T>A	p.Asp458Glu	missense	Exon 6 of 6	NP_066962.2
	UGT2B4	NM_001297616.2		c.966T>A	p.Asp322Glu	missense	Exon 7 of 7	NP_001284545.1
	UGT2B4	NM_001297615.2		c.*44T>A		3_prime_UTR	Exon 5 of 5	NP_001284544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B4	ENST00000305107.7	TSL:1 MANE Select	c.1374T>A	p.Asp458Glu	missense	Exon 6 of 6	ENSP00000305221.6
	UGT2B4	ENST00000512583.5	TSL:1	c.*44T>A		3_prime_UTR	Exon 5 of 5	ENSP00000421290.1
	UGT2B4	ENST00000506580.5	TSL:3	n.936T>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30353 AN: 151846 Hom.: 3262 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.199 AC: 50090 AN: 251082 AF XY: 0.194

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.229 AC: 335067 AN: 1461596 Hom.: 41399 Cov.: 33 AF XY: 0.224 AC XY: 163220 AN XY: 727112

African (AFR) AF: 0.141 AC: 4705 AN: 33472

American (AMR) AF: 0.284 AC: 12713 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4346 AN: 26132

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39698

South Asian (SAS) AF: 0.0951 AC: 8203 AN: 86250

European-Finnish (FIN) AF: 0.212 AC: 11321 AN: 53412

Middle Eastern (MID) AF: 0.177 AC: 1021 AN: 5758

European-Non Finnish (NFE) AF: 0.252 AC: 280468 AN: 1111786

Other (OTH) AF: 0.203 AC: 12271 AN: 60376

GnomAD4 genome AF: 0.200 AC: 30380 AN: 151964 Hom.: 3267 Cov.: 31 AF XY: 0.195 AC XY: 14481 AN XY: 74270

African (AFR) AF: 0.149 AC: 6199 AN: 41470

American (AMR) AF: 0.229 AC: 3490 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5176

South Asian (SAS) AF: 0.0949 AC: 457 AN: 4818

European-Finnish (FIN) AF: 0.212 AC: 2245 AN: 10566

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16714 AN: 67906

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.192 Hom.: 1021

Bravo AF: 0.201

TwinsUK AF: 0.268 AC: 994

ALSPAC AF: 0.257 AC: 989

ESP6500AA AF: 0.143 AC: 628

ESP6500EA AF: 0.238 AC: 2045

ExAC AF: 0.193 AC: 23467

Asia WGS AF: 0.0830 AC: 289 AN: 3476

EpiCase AF: 0.236

EpiControl AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.93
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.024	D
Polyphen		0.39	B
Vest4		0.062
MutPred		0.29		Loss of helix (P = 0.0167)
MPC		0.077
ClinPred		0.091	T
GERP RS		-3.8
Varity_R		0.31
gMVP		0.17
Mutation Taster		=96/4	polymorphism (auto)

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: rs13119049; hg19: chr4-70346565; COSMIC: COSV59316617; COSMIC: COSV59316617;