4-68647289-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001076.4(UGT2B15):c.1408C>T(p.Arg470Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,613,910 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R470S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (52 hom.)
• Consequence: UGT2B15 NM_001076.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.478

Genes affected

UGT2B15 (HGNC:12546): (UDP glucuronosyltransferase family 2 member B15) This gene encodes a glycosyltransferase that is invovled in the metabolism and elimination of toxic compounts, both endogenous and of xenobiotic origin. This gene plays a role in the regulation of estrogens and androgens. This locus is present in a cluster of similar genes and pseudogenes on chromosome 4. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023572743).
• BP6: Variant 4-68647289-G-A is Benign according to our data. Variant chr4-68647289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 782091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B15	NM_001076.4	c.1408C>T	p.Arg470Cys	missense_variant	6/6	ENST00000338206.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B15	ENST00000338206.6	c.1408C>T	p.Arg470Cys	missense_variant	6/6	1	NM_001076.4	P1

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 493 AN: 152078 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00278 AC: 700 AN: 251394 Hom.: 7 AF XY: 0.00297 AC XY: 403 AN XY: 135866

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000751

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00496

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00391 AC: 5712 AN: 1461716 Hom.: 52 Cov.: 33 AF XY: 0.00386 AC XY: 2807 AN XY: 727174

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.00101

Gnomad4 NFE exome AF: 0.00472

Gnomad4 OTH exome AF: 0.00351

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152194 Hom.: 3 Cov.: 32 AF XY: 0.00274 AC XY: 204 AN XY: 74412

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00579

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00435 Hom.: 2

Bravo AF: 0.00328

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00279 AC: 339

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00622

EpiControl AF: 0.00522

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 01, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	UGT2B15: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.024	T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	4.5	H
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.51
Sift	Benign	0.030	D
Sift4G	Uncertain	0.025	D
Polyphen		0.86	P
Vest4		0.49
MVP		0.61
MPC		0.025
ClinPred		0.14	T
GERP RS		3.0
Varity_R		0.67
gMVP		0.28

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: rs147164238; hg19: chr4-69513007;