chr4-68537809-C-A

Variant names:

• chr4-68537809-C-A
• rs757359658
• NM_001077.4:c.1409G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001077.4(UGT2B17):​c.1409G>T​(p.Arg470Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000806 in 1,253,090 control chromosomes in the GnomAD database, including 35 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R470H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000081 (35 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• Publications: 1 publications found

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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077.4. 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
	UGT2B17	NM_001077.4	MANE Select	c.1409G>T	p.Arg470Leu	missense	Exon 7 of 7	NP_001068.1	O75795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	ENST00000317746.3	TSL:1 MANE Select	c.1409G>T	p.Arg470Leu	missense	Exon 7 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1409G>T	p.Arg470Leu	missense	Exon 6 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1277G>T	p.Arg426Leu	missense	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 126322 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 21 AN: 202878 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000806 AC: 101 AN: 1253090 Hom.: 35 Cov.: 30 AF XY: 0.000115 AC XY: 71 AN XY: 619242

African (AFR) AF: 0.00 AC: 0 AN: 30952

American (AMR) AF: 0.00 AC: 0 AN: 38296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22654

East Asian (EAS) AF: 0.00 AC: 0 AN: 10794

South Asian (SAS) AF: 0.00162 AC: 93 AN: 57262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4896

European-Non Finnish (NFE) AF: 0.00000703 AC: 7 AN: 995246

Other (OTH) AF: 0.0000196 AC: 1 AN: 51044

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 126322 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 60206

African (AFR) AF: 0.00 AC: 0 AN: 36996

American (AMR) AF: 0.00 AC: 0 AN: 12286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2974

East Asian (EAS) AF: 0.00 AC: 0 AN: 1322

South Asian (SAS) AF: 0.00 AC: 0 AN: 2728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59730

Other (OTH) AF: 0.00 AC: 0 AN: 1698

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000135 AC: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	4.6	H
PhyloP100		5.3
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.59
MutPred		0.73		Loss of MoRF binding (P = 0.0173)
MVP		0.55
MPC		1.8
ClinPred		0.98	D
GERP RS		2.0
Varity_R		0.61
gMVP		0.42
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs757359658; hg19: chr4-69403527;