chr4-69488857-C-T

Variant names:

• chr4-69488857-C-T
• rs2013562
• NM_021139.3:c.1002+582G>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.1002+582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,644 control chromosomes in the GnomAD database, including 13,288 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 0.41 (13288 hom., cov: 30)
• Consequence: UGT2B4 NM_021139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_021139.3	c.1002+582G>A		intron_variant	Intron 3 of 5	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2	c.594+582G>A		intron_variant	Intron 4 of 6		NP_001284545.1
UGT2B4	NM_001297615.2	c.1002+582G>A		intron_variant	Intron 3 of 4		NP_001284544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7	c.1002+582G>A		intron_variant	Intron 3 of 5	1	NM_021139.3	ENSP00000305221.6
UGT2B4	ENST00000512583.5	c.1002+582G>A		intron_variant	Intron 3 of 4	1		ENSP00000421290.1
UGT2B4	ENST00000502655.5	n.879+582G>A		intron_variant	Intron 4 of 5	5
UGT2B4	ENST00000506580.5	n.784+582G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61640 AN: 151526 Hom.: 13283 Cov.: 30

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.407 AC: 61673 AN: 151644 Hom.: 13288 Cov.: 30 AF XY: 0.415 AC XY: 30753 AN XY: 74066

African (AFR) AF: 0.276 AC: 11408 AN: 41332

American (AMR) AF: 0.485 AC: 7379 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1504 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2388 AN: 5106

South Asian (SAS) AF: 0.618 AC: 2967 AN: 4804

European-Finnish (FIN) AF: 0.458 AC: 4800 AN: 10484

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29769 AN: 67924

Other (OTH) AF: 0.421 AC: 886 AN: 2106

Alfa AF: 0.431 Hom.: 26551

Bravo AF: 0.396

Asia WGS AF: 0.498 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.21
PhyloP100		-0.46
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: rs2013562; hg19: chr4-70354575;