4-69489575-GA-G

Position:

• chr4-69489575-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_021139.3(UGT2B4):​c.871-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,595,084 control chromosomes in the GnomAD database, including 35 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: UGT2B4 NM_021139.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 4-69489575-GA-G is Benign according to our data. Variant chr4-69489575-GA-G is described in ClinVar as [Benign]. Clinvar id is 717904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00146 (221/151202) while in subpopulation EAS AF= 0.041 (210/5128). AF 95% confidence interval is 0.0364. There are 7 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B4	NM_021139.3	c.871-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000305107.7
UGT2B4	NM_001297615.2	c.871-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UGT2B4	NM_001297616.2	c.463-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B4	ENST00000305107.7	c.871-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021139.3	P1

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 222 AN: 151084 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0411

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00297 AC: 697 AN: 234660 Hom.: 14 AF XY: 0.00278 AC XY: 354 AN XY: 127550

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000337

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0399

Gnomad SAS exome AF: 0.000398

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000276

Gnomad OTH exome AF: 0.00194

GnomAD4 exome AF: 0.00118 AC: 1702 AN: 1443882 Hom.: 28 Cov.: 31 AF XY: 0.00112 AC XY: 806 AN XY: 718510

Gnomad4 AFR exome AF: 0.0000314

Gnomad4 AMR exome AF: 0.0000500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0386

Gnomad4 SAS exome AF: 0.000514

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.0000190

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00146 AC: 221 AN: 151202 Hom.: 7 Cov.: 32 AF XY: 0.00163 AC XY: 120 AN XY: 73796

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000954

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00172

EpiCase AF: 0.000111

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 26, 2018

- -

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;