chr4-68537870-G-A

Variant names:

• chr4-68537870-G-A
• rs72551385
• NM_001077.4:c.1348C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001077.4(UGT2B17):​c.1348C>T​(p.His450Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,371,496 control chromosomes in the GnomAD database, including 718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (345 hom., cov: 20)
  • Exomes 𝑓: 0.0013 (373 hom.)
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 8.86
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005250871).
• BP6: Variant 4-68537870-G-A is Benign according to our data. Variant chr4-68537870-G-A is described in ClinVar as Benign. ClinVar VariationId is 789998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (1746/126160) while in subpopulation AFR AF = 0.0451 (1666/36914). AF 95% confidence interval is 0.0433. There are 345 homozygotes in GnomAd4. There are 820 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 345 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.1348C>T	p.His450Tyr	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.1348C>T	p.His450Tyr	missense	Exon 7 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1348C>T	p.His450Tyr	missense	Exon 6 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1216C>T	p.His406Tyr	missense	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 1741 AN: 126092 Hom.: 343 Cov.: 20

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00488

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: 0.000117

Gnomad OTH AF: 0.00759

GnomAD2 exomes AF: 0.00389 AC: 773 AN: 198940 AF XY: 0.00278

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000599

Gnomad OTH exome AF: 0.00174

GnomAD4 exome AF: 0.00134 AC: 1667 AN: 1245336 Hom.: 373 Cov.: 29 AF XY: 0.00113 AC XY: 693 AN XY: 615108

African (AFR) AF: 0.0452 AC: 1386 AN: 30672

American (AMR) AF: 0.00261 AC: 97 AN: 37212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22390

East Asian (EAS) AF: 0.00 AC: 0 AN: 10758

South Asian (SAS) AF: 0.000107 AC: 6 AN: 56178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4878

European-Non Finnish (NFE) AF: 0.0000333 AC: 33 AN: 990784

Other (OTH) AF: 0.00286 AC: 145 AN: 50706

GnomAD4 genome AF: 0.0138 AC: 1746 AN: 126160 Hom.: 345 Cov.: 20 AF XY: 0.0136 AC XY: 820 AN XY: 60198

African (AFR) AF: 0.0451 AC: 1666 AN: 36914

American (AMR) AF: 0.00488 AC: 60 AN: 12300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2976

East Asian (EAS) AF: 0.00 AC: 0 AN: 1324

South Asian (SAS) AF: 0.00 AC: 0 AN: 2734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000117 AC: 7 AN: 59642

Other (OTH) AF: 0.00752 AC: 13 AN: 1728

Alfa AF: 0.00749 Hom.: 23

ESP6500AA AF: 0.0447 AC: 187

ESP6500EA AF: 0.000382 AC: 3

ExAC AF: 0.00492 AC: 505

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	UGT2B17-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.011
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		8.9
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Vest4		0.34
MVP		0.55
MPC		1.8
ClinPred		0.10	T
GERP RS		2.9
Varity_R		0.43
gMVP		0.28
Mutation Taster		=86/14	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

Other links and lift over

dbSNP: rs72551385; hg19: chr4-69403588; COSMIC: COSV104619461;