4-68550838-T-C

Position:

• chr4-68550838-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001077.4(UGT2B17):​c.1152A>G​(p.Ala384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,303,652 control chromosomes in the GnomAD database, including 140,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (10648 hom., cov: 20)
  • Exomes 𝑓: 0.31 (129540 hom.)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

Genes affected

UGT2B17 (HGNC:12547): (UDP glucuronosyltransferase family 2 member B17) This gene encodes a member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Copy number variation in this gene is associated with susceptibility to osteoporosis.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-68550838-T-C is Benign according to our data. Variant chr4-68550838-T-C is described in ClinVar as [Benign]. Clinvar id is 3059332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B17	NM_001077.4	c.1152A>G	p.Ala384=	synonymous_variant	6/7	ENST00000317746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B17	ENST00000317746.3	c.1152A>G	p.Ala384=	synonymous_variant	6/7	1	NM_001077.4	P1
UGT2B17	ENST00000684088.1	c.402A>G	p.Ala134=	synonymous_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 32978 AN: 124396 Hom.: 10644 Cov.: 20

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.295 AC: 55653 AN: 188972 Hom.: 20352 AF XY: 0.291 AC XY: 29476 AN XY: 101340

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.00591

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.307 AC: 362273 AN: 1179192 Hom.: 129540 Cov.: 32 AF XY: 0.306 AC XY: 178413 AN XY: 582660

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.00464

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.265 AC: 32991 AN: 124460 Hom.: 10648 Cov.: 20 AF XY: 0.269 AC XY: 16004 AN XY: 59400

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.234

Alfa AF: 0.0314 Hom.: 71

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

UGT2B17-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.30

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: rs13102139; hg19: chr4-69416556; COSMIC: COSV58500792;