4-69200706-T-C

Variant names:

• chr4-69200706-T-C
• rs201914215
• NM_001073.3:c.1324A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001073.3(UGT2B11):​c.1324A>G​(p.Ile442Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.938
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046341717).
• BP6: Variant 4-69200706-T-C is Benign according to our data. Variant chr4-69200706-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2681634.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1324A>G	p.Ile442Val	missense	Exon 6 of 6	NP_001064.1	O75310
	LOC105377267	NR_136191.1		n.484+128T>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.1324A>G	p.Ile442Val	missense	Exon 6 of 6	ENSP00000387683.1	O75310
	ENSG00000250696	ENST00000766440.1		n.479T>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000250696	ENST00000504301.5	TSL:5	n.484+128T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 247874 AF XY: 0.0000149

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000535

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000156 AC: 222 AN: 1419414 Hom.: 0 Cov.: 33 AF XY: 0.000194 AC XY: 137 AN XY: 705938

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

African (AFR) AF: 0.000153 AC: 5 AN: 32772

American (AMR) AF: 0.000283 AC: 12 AN: 42454

Ashkenazi Jewish (ASJ) AF: 0.000118 AC: 3 AN: 25506

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39238

South Asian (SAS) AF: 0.0000711 AC: 6 AN: 84378

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.000173 AC: 186 AN: 1077678

Other (OTH) AF: 0.0000850 AC: 5 AN: 58808

⚠️ 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 Cov.: 32

Alfa AF: 0.0000605 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.000173 AC: 21

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.16
DANN	Benign	0.78
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.94
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.055
Sift	Benign	0.28	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.21
MPC		0.010
ClinPred		0.075	T
GERP RS		0.36
Varity_R		0.036
gMVP		0.096
Mutation Taster		=88/12	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: rs201914215; hg19: chr4-70066424; COSMIC: COSV71424118; COSMIC: COSV71424118;