4-69204497-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001073.3(UGT2B11):​c.1243T>C​(p.Leu415Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: UGT2B11 NM_001073.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-2.75 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.1243T>C	p.Leu415Leu	synonymous_variant	Exon 5 of 6	ENST00000446444.2	NP_001064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.1243T>C	p.Leu415Leu	synonymous_variant	Exon 5 of 6	1	NM_001073.3	ENSP00000387683.1
UGT2B11	ENST00000513315.1	n.367T>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
ENSG00000250696	ENST00000504301.5	n.484+3919A>G		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1	n.272+3213A>G		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151734 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000518 AC: 13 AN: 251050 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135702

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1460428 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726554

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151852 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74186

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.38

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: rs140410140; hg19: chr4-70070215; COSMIC: COSV101485255;