4-68647129-T-G

Variant names:

• chr4-68647129-T-G
• rs4148269
• NM_001076.4:c.1568A>C

Variant summary

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

The NM_001076.4(UGT2B15):​c.1568A>C​(p.Lys523Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,613,218 control chromosomes in the GnomAD database, including 306,390 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.49 (21143 hom., cov: 32)
  • Exomes 𝑓: 0.61 (285247 hom.)
• Consequence: UGT2B15 NM_001076.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=3.9870465E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B15	NM_001076.4	c.1568A>C	p.Lys523Thr	missense_variant	Exon 6 of 6	ENST00000338206.6	NP_001067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B15	ENST00000338206.6	c.1568A>C	p.Lys523Thr	missense_variant	Exon 6 of 6	1	NM_001076.4	ENSP00000341045.5

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73997 AN: 151806 Hom.: 21142 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.470

GnomAD3 exomes AF: 0.550 AC: 137921 AN: 250942 Hom.: 41081 AF XY: 0.556 AC XY: 75477 AN XY: 135636

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.554

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.173

Gnomad SAS exome AF: 0.523

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.613 AC: 895733 AN: 1461290 Hom.: 285247 Cov.: 75 AF XY: 0.611 AC XY: 444472 AN XY: 726932

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.653

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.487 AC: 74024 AN: 151928 Hom.: 21143 Cov.: 32 AF XY: 0.485 AC XY: 35988 AN XY: 74248

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.468

Alfa AF: 0.575 Hom.: 11457

Bravo AF: 0.463

TwinsUK AF: 0.650 AC: 2411

ALSPAC AF: 0.654 AC: 2519

ESP6500AA AF: 0.224 AC: 989

ESP6500EA AF: 0.633 AC: 5436

ExAC AF: 0.545 AC: 66222

Asia WGS AF: 0.363 AC: 1265 AN: 3478

EpiCase AF: 0.634

EpiControl AF: 0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.011
DANN	Benign	0.15
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.043	T
MetaRNN	Benign	0.0000040	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.045	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.020
ClinPred		0.0025	T
GERP RS		-0.32
Varity_R		0.028
gMVP		0.093

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: rs4148269; hg19: chr4-69512847; COSMIC: COSV57734210;