4-68647129-T-G

Variant names:

• chr4-68647129-T-G
• rs4148269
• NM_001076.4:c.1568A>C
• UGT2B15 p.Lys523Thr

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076.4. 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
	UGT2B15	NM_001076.4	MANE Select	c.1568A>C	p.Lys523Thr	missense	Exon 6 of 6	NP_001067.2	P54855

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B15	ENST00000338206.6	TSL:1 MANE Select	c.1568A>C	p.Lys523Thr	missense	Exon 6 of 6	ENSP00000341045.5	P54855
	UGT2B15	ENST00000962480.1		c.1436A>C	p.Lys479Thr	missense	Exon 5 of 5	ENSP00000632539.1
	UGT2B15	ENST00000871508.1		c.1316A>C	p.Lys439Thr	missense	Exon 6 of 6	ENSP00000541567.1

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

GnomAD2 exomes AF: 0.550 AC: 137921 AN: 250942 AF XY: 0.556

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 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

African (AFR) AF: 0.189 AC: 6325 AN: 33450

American (AMR) AF: 0.549 AC: 24530 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 16050 AN: 26122

East Asian (EAS) AF: 0.171 AC: 6787 AN: 39698

South Asian (SAS) AF: 0.521 AC: 44913 AN: 86178

European-Finnish (FIN) AF: 0.629 AC: 33588 AN: 53408

Middle Eastern (MID) AF: 0.548 AC: 3158 AN: 5760

European-Non Finnish (NFE) AF: 0.653 AC: 725914 AN: 1111612

Other (OTH) AF: 0.571 AC: 34468 AN: 60368

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

African (AFR) AF: 0.209 AC: 8677 AN: 41456

American (AMR) AF: 0.510 AC: 7776 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2140 AN: 3462

East Asian (EAS) AF: 0.179 AC: 926 AN: 5178

South Asian (SAS) AF: 0.519 AC: 2491 AN: 4800

European-Finnish (FIN) AF: 0.617 AC: 6508 AN: 10546

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43755 AN: 67924

Other (OTH) AF: 0.468 AC: 989 AN: 2112

Alfa AF: 0.575 Hom.: 11457

Bravo AF: 0.463

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 v4.9

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
PhyloP100		-1.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Varity_R		0.028
gMVP		0.093
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4148269;

hg19: chr4-69512847;

COSMIC: COSV57734210;