chr4-68670366-A-C

Position:

• chr4-68670366-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001076.4(UGT2B15):​c.253T>G​(p.Tyr85Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,612,884 control chromosomes in the GnomAD database, including 195,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.53 (21412 hom., cov: 33)
  • Exomes 𝑓: 0.49 (174266 hom.)
• Consequence: UGT2B15 NM_001076.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9567053E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B15	NM_001076.4	c.253T>G	p.Tyr85Asp	missense_variant	1/6	ENST00000338206.6	NP_001067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B15	ENST00000338206.6	c.253T>G	p.Tyr85Asp	missense_variant	1/6	1	NM_001076.4	ENSP00000341045	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79828 AN: 151948 Hom.: 21370 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.512 AC: 127728 AN: 249434 Hom.: 33466 AF XY: 0.501 AC XY: 67691 AN XY: 135096

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.559

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.486 AC: 709700 AN: 1460818 Hom.: 174266 Cov.: 62 AF XY: 0.483 AC XY: 351324 AN XY: 726708

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.526 AC: 79925 AN: 152066 Hom.: 21412 Cov.: 33 AF XY: 0.528 AC XY: 39261 AN XY: 74332

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.533

Alfa AF: 0.486 Hom.: 21657

Bravo AF: 0.531

TwinsUK AF: 0.469 AC: 1740

ALSPAC AF: 0.470 AC: 1812

ESP6500AA AF: 0.576 AC: 2534

ESP6500EA AF: 0.465 AC: 3995

ExAC AF: 0.502 AC: 60912

Asia WGS AF: 0.478 AC: 1665 AN: 3478

EpiCase AF: 0.474

EpiControl AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.15
DANN	Benign	0.21
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.0054	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	4.5	N
REVEL	Benign	0.050
Sift	Benign	0.67	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.052
ClinPred		0.018	T
GERP RS		2.6
Varity_R		0.057
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: rs1902023; hg19: chr4-69536084; COSMIC: COSV57733019;