4-69493127-T-G

Variant names:

• chr4-69493127-T-G
• rs17671289
• NM_021139.3:c.870+566A>C

Variant summary

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

The NM_021139.3(UGT2B4):​c.870+566A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,926 control chromosomes in the GnomAD database, including 3,874 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 0.21 (3874 hom., cov: 31)
• Consequence: UGT2B4 NM_021139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B4	NM_021139.3	MANE Select	c.870+566A>C		intron	N/A	NP_066962.2	P06133-1
	UGT2B4	NM_001297616.2		c.462+566A>C		intron	N/A	NP_001284545.1	P06133-2
	UGT2B4	NM_001297615.2		c.870+566A>C		intron	N/A	NP_001284544.1	P06133-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B4	ENST00000305107.7	TSL:1 MANE Select	c.870+566A>C		intron	N/A	ENSP00000305221.6	P06133-1
	UGT2B4	ENST00000512583.5	TSL:1	c.870+566A>C		intron	N/A	ENSP00000421290.1	P06133-3
	UGT2B4	ENST00000968901.1		c.870+566A>C		intron	N/A	ENSP00000638960.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31589 AN: 151810 Hom.: 3881 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.208 AC: 31591 AN: 151926 Hom.: 3874 Cov.: 31 AF XY: 0.215 AC XY: 15959 AN XY: 74204

African (AFR) AF: 0.0999 AC: 4147 AN: 41510

American (AMR) AF: 0.239 AC: 3630 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3472

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5174

South Asian (SAS) AF: 0.306 AC: 1472 AN: 4812

European-Finnish (FIN) AF: 0.351 AC: 3702 AN: 10544

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16718 AN: 67898

Other (OTH) AF: 0.208 AC: 439 AN: 2108

Alfa AF: 0.197 Hom.: 1585

Bravo AF: 0.193

Asia WGS AF: 0.159 AC: 553 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.48
PhyloP100		-0.54
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: rs17671289; hg19: chr4-70358845;