Genetic Variant UGT2B4:c.871-6delT (chr4-69489575-GA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_021139.3(UGT2B4):c.871-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 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, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.77

Variant links:

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]

UGT2B4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_021139.3 link	c.871-6delT	splice_region_variant, intron_variant	Intron 2 of 5	ENST00000305107.7	NP_066962.2	P06133-1
UGT2B4	NM_001297616.2 link	c.463-6delT	splice_region_variant, intron_variant	Intron 3 of 6		NP_001284545.1	P06133-2
UGT2B4	NM_001297615.2 link	c.871-6delT	splice_region_variant, intron_variant	Intron 2 of 4		NP_001284544.1	P06133-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7 link	c.871-6delT		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_021139.3	ENSP00000305221.6		P06133-1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

222

AN:

151084

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00297

AC:

697

AN:

234660

AF XY:

0.00278

show subpopulations

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 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.:

Cov.:

AF XY:

0.00112

AC XY:

806

AN XY:

718510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

AC:

AN:

31812

Gnomad4 AMR exome

AF:

0.0000500

AC:

AN:

40002

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25562

Gnomad4 EAS exome

AF:

0.0386

AC:

1521

AN:

39378

Gnomad4 SAS exome

AF:

0.000514

AC:

AN:

83650

Gnomad4 FIN exome

AF:

0.0000378

AC:

AN:

52870

Gnomad4 NFE exome

AF:

0.0000190

AC:

AN:

1105456

Gnomad4 Remaining exome

AF:

0.00187

AC:

111

AN:

59504

Heterozygous variant carriers

173

259

346

432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00146

AC:

221

AN:

151202

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

120

AN XY:

73796

show subpopulations

Gnomad4 AFR

AF:

0.0000243

AC:

0.0000242718

AN:

0.0000242718

Gnomad4 AMR

AF:

0.0000659

AC:

0.0000658762

AN:

0.0000658762

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.0410

AC:

0.0409516

AN:

0.0409516

Gnomad4 SAS

AF:

0.00125

AC:

0.00125104

AN:

0.00125104

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000148

AC:

0.0000147571

AN:

0.0000147571

Gnomad4 OTH

AF:

0.000954

AC:

0.000954198

AN:

0.000954198

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.00172

EpiCase

AF:

0.000111

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over