chr4-69214257-A-G

Position:

• chr4-69214257-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000446444.2(UGT2B11):​c.466T>C​(p.Cys156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,064 control chromosomes in the GnomAD database, including 12,371 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C156Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.16 (2307 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10064 hom.)
• Consequence: UGT2B11 ENST00000446444.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030103326).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.466T>C	p.Cys156Arg	missense_variant	1/6	ENST00000446444.2	NP_001064.1
LOC105377267	NR_136191.1	n.680-216A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.466T>C	p.Cys156Arg	missense_variant	1/6	1	NM_001073.3	ENSP00000387683	P1
	ENST00000504301.5	n.567-216A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000505646.1	n.355-216A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23980 AN: 151640 Hom.: 2304 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.137 AC: 34404 AN: 251136 Hom.: 2928 AF XY: 0.133 AC XY: 18108 AN XY: 135716

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0392

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.106 AC: 155580 AN: 1461306 Hom.: 10064 Cov.: 33 AF XY: 0.107 AC XY: 77929 AN XY: 726948

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0623

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.0902

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.158 AC: 24016 AN: 151758 Hom.: 2307 Cov.: 32 AF XY: 0.163 AC XY: 12119 AN XY: 74164

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.0972

Gnomad4 OTH AF: 0.148

Alfa AF: 0.113 Hom.: 906

Bravo AF: 0.159

TwinsUK AF: 0.0793 AC: 294

ALSPAC AF: 0.0944 AC: 364

ESP6500AA AF: 0.256 AC: 1129

ESP6500EA AF: 0.0961 AC: 826

ExAC AF: 0.137 AC: 16592

Asia WGS AF: 0.112 AC: 390 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.052
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.097	N
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.1	H
MutationTaster	Benign	0.0050	P
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-9.9	D
REVEL	Benign	0.22
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.21
MPC		0.047
ClinPred		0.15	T
GERP RS		2.0
Varity_R		0.59
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7697037; hg19: chr4-70079975; COSMIC: COSV71423216; COSMIC: COSV71423216;