chr4-69204649-C-T

Variant names:

• chr4-69204649-C-T
• rs146890806
• NM_001073.3:c.1091G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001073.3(UGT2B11):​c.1091G>A​(p.Gly364Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,611,184 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (44 hom.)
• Consequence: UGT2B11 NM_001073.3 missense, splice_region
• Scores: Splicing: ADA: 0.07658
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

Genes affected

UGT2B11 (HGNC:12545): (UDP glucuronosyltransferase family 2 member B11) Enables glucuronosyltransferase activity. Involved in estrogen metabolic process and xenobiotic glucuronidation. 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]

ENSG00000250696 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032261103).
• BP6: Variant 4-69204649-C-T is Benign according to our data. Variant chr4-69204649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.1091G>A	p.Gly364Asp	missense_variant, splice_region_variant	Exon 5 of 6	ENST00000446444.2	NP_001064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.1091G>A	p.Gly364Asp	missense_variant, splice_region_variant	Exon 5 of 6	1	NM_001073.3	ENSP00000387683.1
UGT2B11	ENST00000513315.1	n.215G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	3
ENSG00000250696	ENST00000504301.5	n.484+4071C>T		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1	n.272+3365C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00548 AC: 830 AN: 151496 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00330

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00833

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00553 AC: 1362 AN: 246212 AF XY: 0.00554

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00242

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.00795

Gnomad OTH exome AF: 0.00553

GnomAD4 exome AF: 0.00684 AC: 9979 AN: 1459570 Hom.: 44 Cov.: 31 AF XY: 0.00682 AC XY: 4955 AN XY: 726160

Gnomad4 AFR exome AF: 0.00114 AC: 38 AN: 33294

Gnomad4 AMR exome AF: 0.00274 AC: 122 AN: 44502

Gnomad4 ASJ exome AF: 0.00261 AC: 68 AN: 26026

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39612

Gnomad4 SAS exome AF: 0.00194 AC: 167 AN: 86164

Gnomad4 FIN exome AF: 0.0127 AC: 679 AN: 53380

Gnomad4 NFE exome AF: 0.00773 AC: 8584 AN: 1110626

Gnomad4 Remaining exome AF: 0.00526 AC: 317 AN: 60222

GnomAD4 genome AF: 0.00547 AC: 829 AN: 151614 Hom.: 2 Cov.: 32 AF XY: 0.00563 AC XY: 417 AN XY: 74050

Gnomad4 AFR AF: 0.00147 AC: 0.00147307 AN: 0.00147307

Gnomad4 AMR AF: 0.00330 AC: 0.00329554 AN: 0.00329554

Gnomad4 ASJ AF: 0.00173 AC: 0.0017321 AN: 0.0017321

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00125 AC: 0.00124792 AN: 0.00124792

Gnomad4 FIN AF: 0.0126 AC: 0.0125899 AN: 0.0125899

Gnomad4 NFE AF: 0.00834 AC: 0.00833555 AN: 0.00833555

Gnomad4 OTH AF: 0.00237 AC: 0.00237192 AN: 0.00237192

Alfa AF: 0.00476 Hom.: 0

Bravo AF: 0.00444

ESP6500AA AF: 0.00192 AC: 8

ESP6500EA AF: 0.00575 AC: 47

ExAC AF: 0.00568 AC: 682

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UGT2B11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	4.2	H
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.67
MPC		0.064
ClinPred		0.065	T
GERP RS		2.0
Varity_R		0.93
gMVP		0.41
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.077
dbscSNV1_RF	Benign	0.43
SpliceAI score (max)		0.13		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: rs146890806; hg19: chr4-70070367; COSMIC: COSV104716960;