chr4-69488760-C-T

Variant names:

• chr4-69488760-C-T
• rs2013573
• NM_021139.3:c.1002+679G>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+679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,858 control chromosomes in the GnomAD database, including 1,955 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 0.14 (1955 hom., cov: 31)
• Consequence: UGT2B4 NM_021139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_021139.3	c.1002+679G>A		intron_variant	Intron 3 of 5	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2	c.594+679G>A		intron_variant	Intron 4 of 6		NP_001284545.1
UGT2B4	NM_001297615.2	c.1002+679G>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+679G>A		intron_variant	Intron 3 of 5	1	NM_021139.3	ENSP00000305221.6
UGT2B4	ENST00000512583.5	c.1002+679G>A		intron_variant	Intron 3 of 4	1		ENSP00000421290.1
UGT2B4	ENST00000502655.5	n.879+679G>A		intron_variant	Intron 4 of 5	5
UGT2B4	ENST00000506580.5	n.784+679G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21021 AN: 151738 Hom.: 1956 Cov.: 31

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.138 AC: 21014 AN: 151858 Hom.: 1955 Cov.: 31 AF XY: 0.134 AC XY: 9925 AN XY: 74210

African (AFR) AF: 0.0377 AC: 1562 AN: 41472

American (AMR) AF: 0.116 AC: 1758 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 487 AN: 3466

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5160

South Asian (SAS) AF: 0.0823 AC: 395 AN: 4802

European-Finnish (FIN) AF: 0.180 AC: 1898 AN: 10520

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14375 AN: 67910

Other (OTH) AF: 0.141 AC: 298 AN: 2106

Alfa AF: 0.181 Hom.: 5476

Bravo AF: 0.130

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		-0.65
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: rs2013573; hg19: chr4-70354478;