chr4-68537856-C-T

Variant names:

• chr4-68537856-C-T
• rs746870450
• NM_001077.4:c.1362G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001077.4(UGT2B17):​c.1362G>A​(p.Pro454Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,249,308 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.000022 (8 hom.)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.11
• Publications: 0 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 4-68537856-C-T is Benign according to our data. Variant chr4-68537856-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3036282.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.11 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 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.1362G>A	p.Pro454Pro	synonymous	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.1362G>A	p.Pro454Pro	synonymous	Exon 7 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1362G>A	p.Pro454Pro	synonymous	Exon 6 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1230G>A	p.Pro410Pro	synonymous	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.0000348 AC: 7 AN: 200936 AF XY: 0.0000371

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000993

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000224 AC: 28 AN: 1249308 Hom.: 8 Cov.: 29 AF XY: 0.0000259 AC XY: 16 AN XY: 617188

African (AFR) AF: 0.00 AC: 0 AN: 30840

American (AMR) AF: 0.000317 AC: 12 AN: 37828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22488

East Asian (EAS) AF: 0.00 AC: 0 AN: 10772

South Asian (SAS) AF: 0.00 AC: 0 AN: 56638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4894

European-Non Finnish (NFE) AF: 0.0000141 AC: 14 AN: 993162

Other (OTH) AF: 0.0000393 AC: 2 AN: 50854

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UGT2B17-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=97/3	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: rs746870450; hg19: chr4-69403574; COSMIC: COSV58502648;