chr4-68550838-T-C

Variant names:

• chr4-68550838-T-C
• rs13102139
• NM_001077.4:c.1152A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001077.4(UGT2B17):​c.1152A>G​(p.Ala384Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,303,652 control chromosomes in the GnomAD database, including 140,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.27 (10648 hom., cov: 20)
  • Exomes 𝑓: 0.31 (129540 hom.)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.93
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-68550838-T-C is Benign according to our data. Variant chr4-68550838-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059332.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

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.1152A>G	p.Ala384Ala	synonymous	Exon 6 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.1152A>G	p.Ala384Ala	synonymous	Exon 6 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1152A>G	p.Ala384Ala	synonymous	Exon 5 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1020A>G	p.Ala340Ala	synonymous	Exon 4 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 32978 AN: 124396 Hom.: 10644 Cov.: 20

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.295 AC: 55653 AN: 188972 AF XY: 0.291

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.00591

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.307 AC: 362273 AN: 1179192 Hom.: 129540 Cov.: 32 AF XY: 0.306 AC XY: 178413 AN XY: 582660

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

African (AFR) AF: 0.0765 AC: 2315 AN: 30272

American (AMR) AF: 0.504 AC: 17628 AN: 34972

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 4962 AN: 21448

East Asian (EAS) AF: 0.00464 AC: 50 AN: 10784

South Asian (SAS) AF: 0.313 AC: 17244 AN: 55144

European-Finnish (FIN) AF: 0.396 AC: 16387 AN: 41330

Middle Eastern (MID) AF: 0.168 AC: 799 AN: 4764

European-Non Finnish (NFE) AF: 0.311 AC: 289298 AN: 931624

Other (OTH) AF: 0.278 AC: 13590 AN: 48854

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.265 AC: 32991 AN: 124460 Hom.: 10648 Cov.: 20 AF XY: 0.269 AC XY: 16004 AN XY: 59400

African (AFR) AF: 0.0972 AC: 3569 AN: 36716

American (AMR) AF: 0.404 AC: 4846 AN: 11984

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 699 AN: 2948

East Asian (EAS) AF: 0.0113 AC: 15 AN: 1322

South Asian (SAS) AF: 0.278 AC: 731 AN: 2632

European-Finnish (FIN) AF: 0.400 AC: 2957 AN: 7396

Middle Eastern (MID) AF: 0.143 AC: 36 AN: 252

European-Non Finnish (NFE) AF: 0.329 AC: 19327 AN: 58806

Other (OTH) AF: 0.234 AC: 400 AN: 1706

Alfa AF: 0.0314 Hom.: 71

ClinVar

ClinVar submissions

Significance: 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	-0.82
CADD	Benign	0.14
DANN	Benign	0.30
PhyloP100		-1.9
Mutation Taster		=100/0	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: rs13102139; hg19: chr4-69416556; COSMIC: COSV58500792;