rs7697037

Positions:

• chr4-69214257-A-C
• chr4-69214257-A-G

Variant summary

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

The NM_001073.3(UGT2B11):​c.466T>G​(p.Cys156Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2B11 NM_001073.3 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.466T>G	p.Cys156Gly	missense_variant	1/6	ENST00000446444.2	NP_001064.1
LOC105377267	NR_136191.1	n.680-216A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.466T>G	p.Cys156Gly	missense_variant	1/6	1	NM_001073.3	ENSP00000387683	P1
	ENST00000504301.5	n.567-216A>C		intron_variant, non_coding_transcript_variant		5
	ENST00000505646.1	n.355-216A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251136 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461328 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-9.3	D
REVEL	Benign	0.20
Sift	Benign	0.066	T
Sift4G	Benign	0.19	T
Polyphen		0.62	P
Vest4		0.19
MutPred		0.78		Loss of catalytic residue at P155 (P = 0.0154);
MVP		0.67
MPC		0.010
ClinPred		0.79	D
GERP RS		2.0
Varity_R		0.26
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;