4-69214257-A-G

Variant names:

• chr4-69214257-A-G
• rs7697037
• NM_001073.3:c.466T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001073.3(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. 13/21 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 NM_001073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 16 publications found

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 -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 rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.466T>C	p.Cys156Arg	missense_variant	Exon 1 of 6	ENST00000446444.2	NP_001064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.466T>C	p.Cys156Arg	missense_variant	Exon 1 of 6	1	NM_001073.3	ENSP00000387683.1
ENSG00000250696	ENST00000504301.5	n.567-216A>G		intron_variant	Intron 4 of 4	5
ENSG00000250696	ENST00000505646.1	n.355-216A>G		intron_variant	Intron 3 of 3	2
ENSG00000250696	ENST00000766439.1	n.434-216A>G		intron_variant	Intron 3 of 3

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

GnomAD2 exomes AF: 0.137 AC: 34404 AN: 251136 AF XY: 0.133

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 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

African (AFR) AF: 0.268 AC: 8966 AN: 33448

American (AMR) AF: 0.183 AC: 8160 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3004 AN: 26108

East Asian (EAS) AF: 0.0623 AC: 2471 AN: 39666

South Asian (SAS) AF: 0.158 AC: 13619 AN: 86230

European-Finnish (FIN) AF: 0.217 AC: 11607 AN: 53416

Middle Eastern (MID) AF: 0.131 AC: 755 AN: 5762

European-Non Finnish (NFE) AF: 0.0902 AC: 100262 AN: 1111608

Other (OTH) AF: 0.112 AC: 6736 AN: 60372

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

African (AFR) AF: 0.264 AC: 10940 AN: 41412

American (AMR) AF: 0.156 AC: 2362 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3458

East Asian (EAS) AF: 0.0450 AC: 231 AN: 5138

South Asian (SAS) AF: 0.159 AC: 766 AN: 4818

European-Finnish (FIN) AF: 0.214 AC: 2264 AN: 10568

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6600 AN: 67870

Other (OTH) AF: 0.148 AC: 311 AN: 2104

Alfa AF: 0.111 Hom.: 1408

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
PhyloP100		1.1
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
PromoterAI		-0.0067	Neutral
Varity_R		0.59
gMVP		0.57
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7697037; hg19: chr4-70079975; COSMIC: COSV71423216; COSMIC: COSV71423216;