4-68567996-C-T

Variant names:

• chr4-68567996-C-T
• rs34664906
• NM_001077.4:c.489G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001077.4(UGT2B17):​c.489G>A​(p.Glu163Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,379,712 control chromosomes in the GnomAD database, including 206,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (16707 hom., cov: 20)
  • Exomes 𝑓: 0.42 (190272 hom.)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.342

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 4-68567996-C-T is Benign according to our data. Variant chr4-68567996-C-T is described in ClinVar as [Benign]. Clinvar id is 3059548.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.342 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B17	NM_001077.4	c.489G>A	p.Glu163Glu	synonymous_variant	Exon 2 of 7	ENST00000317746.3	NP_001068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B17	ENST00000317746.3	c.489G>A	p.Glu163Glu	synonymous_variant	Exon 2 of 7	1	NM_001077.4	ENSP00000320401.2
UGT2B17	ENST00000684088.1	c.-26-2276G>A		intron_variant	Intron 1 of 4			ENSP00000507374.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 48949 AN: 123728 Hom.: 16699 Cov.: 20

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.380

GnomAD2 exomes AF: 0.427 AC: 86864 AN: 203244 AF XY: 0.420

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.422 AC: 530064 AN: 1255916 Hom.: 190272 Cov.: 34 AF XY: 0.420 AC XY: 260842 AN XY: 621292

African (AFR) AF: 0.311 AC: 9601 AN: 30834

American (AMR) AF: 0.593 AC: 22615 AN: 38134

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 9915 AN: 22782

East Asian (EAS) AF: 0.00593 AC: 64 AN: 10784

South Asian (SAS) AF: 0.359 AC: 21329 AN: 59482

European-Finnish (FIN) AF: 0.492 AC: 20640 AN: 41990

Middle Eastern (MID) AF: 0.333 AC: 1648 AN: 4946

European-Non Finnish (NFE) AF: 0.425 AC: 423523 AN: 995802

Other (OTH) AF: 0.405 AC: 20729 AN: 51162

GnomAD4 genome AF: 0.396 AC: 48977 AN: 123796 Hom.: 16707 Cov.: 20 AF XY: 0.397 AC XY: 23448 AN XY: 59016

African (AFR) AF: 0.318 AC: 11531 AN: 36302

American (AMR) AF: 0.498 AC: 5967 AN: 11990

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1202 AN: 2948

East Asian (EAS) AF: 0.0232 AC: 30 AN: 1294

South Asian (SAS) AF: 0.317 AC: 870 AN: 2748

European-Finnish (FIN) AF: 0.495 AC: 3597 AN: 7262

Middle Eastern (MID) AF: 0.416 AC: 104 AN: 250

European-Non Finnish (NFE) AF: 0.421 AC: 24653 AN: 58606

Other (OTH) AF: 0.375 AC: 638 AN: 1700

Alfa AF: 0.400 Hom.: 1482

Asia WGS AF: 0.201 AC: 383 AN: 1904

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

UGT2B17-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.77
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.34
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs34664906; hg19: chr4-69433714; COSMIC: COSV58502365;