4-69489575-GA-GAA

Variant names:

• chr4-69489575-G-GA
• rs199604241
• NM_021139.3:c.871-6dupT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021139.3(UGT2B4):​c.871-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 1,594,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: UGT2B4 NM_021139.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_021139.3	c.871-6dupT		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2	c.463-6dupT		splice_region_variant, intron_variant	Intron 3 of 6		NP_001284545.1
UGT2B4	NM_001297615.2	c.871-6dupT		splice_region_variant, intron_variant	Intron 2 of 4		NP_001284544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7	c.871-6_871-5insT		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_021139.3	ENSP00000305221.6

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 28 AN: 151084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.0000852 AC: 20 AN: 234660 Hom.: 0 AF XY: 0.0000784 AC XY: 10 AN XY: 127550

Gnomad AFR exome AF: 0.000527

Gnomad AMR exome AF: 0.0000337

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000119

Gnomad SAS exome AF: 0.0000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000643

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.0000533 AC: 77 AN: 1443850 Hom.: 0 Cov.: 31 AF XY: 0.0000557 AC XY: 40 AN XY: 718498

Gnomad4 AFR exome AF: 0.000283

Gnomad4 AMR exome AF: 0.0000750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.0000359

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000479

Gnomad4 OTH exome AF: 0.0000504

GnomAD4 genome AF: 0.000185 AC: 28 AN: 151084 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73668

Gnomad4 AFR AF: 0.000511

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000738

Gnomad4 OTH AF: 0.000482

Bravo AF: 0.000276

EpiCase AF: 0.000111

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs199604241; hg19: chr4-70355293;