4-69200681-T-C

Variant names:

• chr4-69200681-T-C
• rs369662379
• NM_001073.3:c.1349A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001073.3(UGT2B11):​c.1349A>G​(p.His450Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12114844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.1349A>G	p.His450Arg	missense_variant	Exon 6 of 6	ENST00000446444.2	NP_001064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.1349A>G	p.His450Arg	missense_variant	Exon 6 of 6	1	NM_001073.3	ENSP00000387683.1
ENSG00000250696	ENST00000504301.5	n.484+103T>C		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1	n.159+103T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000400 AC: 10 AN: 249726 Hom.: 0 AF XY: 0.0000519 AC XY: 7 AN XY: 134982

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459776 Hom.: 0 Cov.: 33 AF XY: 0.00000964 AC XY: 7 AN XY: 726172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000180

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.57
DANN	Benign	0.45
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.11
Sift	Benign	0.058	T
Sift4G	Benign	0.36	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.49		Loss of catalytic residue at D451 (P = 0.0581);
MVP		0.31
MPC		0.010
ClinPred		0.059	T
GERP RS		-0.040
Varity_R		0.28
gMVP		0.14

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

Other links and lift over

dbSNP: rs369662379; hg19: chr4-70066399;