NM_001073.3:c.1243T>G

Variant names:

• chr4-69204497-A-C
• rs140410140
• NM_001073.3:c.1243T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001073.3(UGT2B11):​c.1243T>G​(p.Leu415Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,612,106 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L415S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.75
• Publications: 4 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:58803):

LOC105377267 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015855849).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001073.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	NM_001073.3	MANE Select	c.1243T>G	p.Leu415Val	missense	Exon 5 of 6	NP_001064.1	O75310
	LOC105377267	NR_136191.1		n.597+3213A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	ENST00000446444.2	TSL:1 MANE Select	c.1243T>G	p.Leu415Val	missense	Exon 5 of 6	ENSP00000387683.1	O75310
	UGT2B11	ENST00000513315.1	TSL:3	n.367T>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000250696	ENST00000504301.5	TSL:5	n.484+3919A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000830 AC: 126 AN: 151734 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000594 AC: 149 AN: 251050 AF XY: 0.000634

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00122 AC: 1786 AN: 1460372 Hom.: 2 Cov.: 31 AF XY: 0.00120 AC XY: 872 AN XY: 726528

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000539 AC: 18 AN: 33374

American (AMR) AF: 0.000134 AC: 6 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86224

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00155 AC: 1717 AN: 1110948

Other (OTH) AF: 0.000431 AC: 26 AN: 60280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000830 AC: 126 AN: 151734 Hom.: 0 Cov.: 32 AF XY: 0.000608 AC XY: 45 AN XY: 74058

African (AFR) AF: 0.000435 AC: 18 AN: 41372

American (AMR) AF: 0.000329 AC: 5 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 67828

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000431 Hom.: 0

Bravo AF: 0.000733

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ExAC AF: 0.000906 AC: 110

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.0030
DANN	Benign	0.42
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		-2.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.079
Sift	Benign	0.40	T
Sift4G	Benign	0.30	T
Polyphen		0.22	B
Vest4		0.15
MVP		0.040
MPC		0.011
ClinPred		0.032	T
GERP RS		-3.9
Varity_R		0.048
gMVP		0.14
Mutation Taster		=93/7	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

Other links and lift over

dbSNP: rs140410140; hg19: chr4-70070215;