4-69489093-G-A

Variant names:

• chr4-69489093-G-A
• rs13111134
• NM_021139.3:c.1002+346C>T

Variant summary

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

The NM_021139.3(UGT2B4):​c.1002+346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,842 control chromosomes in the GnomAD database, including 3,616 homozygotes. In-silico tool predicts 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 (3616 hom., cov: 32)
• Consequence: UGT2B4 NM_021139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 6 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 (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 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.1002+346C>T		intron	N/A	NP_066962.2
	UGT2B4	NM_001297616.2		c.594+346C>T		intron	N/A	NP_001284545.1
	UGT2B4	NM_001297615.2		c.1002+346C>T		intron	N/A	NP_001284544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B4	ENST00000305107.7	TSL:1 MANE Select	c.1002+346C>T		intron	N/A	ENSP00000305221.6
	UGT2B4	ENST00000512583.5	TSL:1	c.1002+346C>T		intron	N/A	ENSP00000421290.1
	UGT2B4	ENST00000502655.5	TSL:5	n.879+346C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30800 AN: 151724 Hom.: 3612 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30815 AN: 151842 Hom.: 3616 Cov.: 32 AF XY: 0.198 AC XY: 14696 AN XY: 74212

African (AFR) AF: 0.110 AC: 4575 AN: 41414

American (AMR) AF: 0.242 AC: 3685 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3466

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5146

South Asian (SAS) AF: 0.0968 AC: 465 AN: 4806

European-Finnish (FIN) AF: 0.228 AC: 2405 AN: 10544

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18312 AN: 67932

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.234 Hom.: 3446

Bravo AF: 0.203

Asia WGS AF: 0.0810 AC: 281 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.59
PhyloP100		-0.28
Mutation Taster		=100/0	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: rs13111134; hg19: chr4-70354811;