rs746870450

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-68537856-C-A
• chr4-68537856-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077.4(UGT2B17):​c.1362G>T​(p.Pro454Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 125,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P454P) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000079 (0 hom., cov: 20)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>T	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>T	p.Pro454Pro	synonymous	Exon 7 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1362G>T	p.Pro454Pro	synonymous	Exon 6 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1230G>T	p.Pro410Pro	synonymous	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes AF: 0.00000794 AC: 1 AN: 125870 Hom.: 0 Cov.: 20

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: 0.0000168

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000794 AC: 1 AN: 125870 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 59976

African (AFR) AF: 0.00 AC: 0 AN: 36868

American (AMR) AF: 0.00 AC: 0 AN: 12190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2966

East Asian (EAS) AF: 0.00 AC: 0 AN: 1326

South Asian (SAS) AF: 0.00 AC: 0 AN: 2722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59572

Other (OTH) AF: 0.00 AC: 0 AN: 1712

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.31
PhyloP100		-2.1

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;