chr4-68568937-A-G

Variant names:

• chr4-68568937-A-G
• rs62317005
• NM_001077.4:c.-64-389T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001077.4(UGT2B17):​c.-64-389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 128,998 control chromosomes in the GnomAD database, including 569 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (569 hom., cov: 26)
• Consequence: UGT2B17 NM_001077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 569 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	NM_001077.4	MANE Select	c.-64-389T>C		intron	N/A	NP_001068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	ENST00000317746.3	TSL:1 MANE Select	c.-64-389T>C		intron	N/A	ENSP00000320401.2
	UGT2B17	ENST00000684088.1		c.-26-3217T>C		intron	N/A	ENSP00000507374.1
	UGT2B17	ENST00000893234.1		c.-453T>C		upstream_gene	N/A	ENSP00000563293.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 15614 AN: 128896 Hom.: 569 Cov.: 26

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00258

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 15614 AN: 128998 Hom.: 569 Cov.: 26 AF XY: 0.120 AC XY: 7494 AN XY: 62550

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0588 AC: 2230 AN: 37918

American (AMR) AF: 0.101 AC: 1288 AN: 12766

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 408 AN: 2972

East Asian (EAS) AF: 0.00259 AC: 8 AN: 3094

South Asian (SAS) AF: 0.131 AC: 438 AN: 3340

European-Finnish (FIN) AF: 0.111 AC: 944 AN: 8530

Middle Eastern (MID) AF: 0.113 AC: 27 AN: 240

European-Non Finnish (NFE) AF: 0.172 AC: 9897 AN: 57576

Other (OTH) AF: 0.122 AC: 219 AN: 1800

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.158 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.51
PhyloP100		-0.62

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: rs62317005; hg19: chr4-69434655;