4-69107234-C-T

Variant names:

• chr4-69107234-C-T
• rs4348159
• NM_001074.4:c.1062C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001074.4(UGT2B7):​c.1062C>T​(p.Tyr354Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,607,194 control chromosomes in the GnomAD database, including 19,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2757 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17022 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.100
• Publications: 17 publications found

Genes affected

UGT2B7 (HGNC:12554): (UDP glucuronosyltransferase family 2 member B7) The protein encoded by this gene belongs to the UDP-glycosyltransferase (UGT) family. UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This protein is localized in the microsome membrane, and has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ENSG00000299782 (HGNC:58802):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-69107234-C-T is Benign according to our data. Variant chr4-69107234-C-T is described in ClinVar as Benign. ClinVar VariationId is 767954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. 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
	UGT2B7	NM_001074.4	MANE Select	c.1062C>T	p.Tyr354Tyr	synonymous	Exon 4 of 6	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.1062C>T	p.Tyr354Tyr	synonymous	Exon 4 of 5	NP_001317648.1	E9PBP8
	UGT2B7	NM_001349568.2		c.315C>T	p.Tyr105Tyr	synonymous	Exon 5 of 7	NP_001336497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.1062C>T	p.Tyr354Tyr	synonymous	Exon 4 of 6	ENSP00000304811.7	P16662
	UGT2B7	ENST00000868341.1		c.1158C>T	p.Tyr386Tyr	synonymous	Exon 5 of 7	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.1062C>T	p.Tyr354Tyr	synonymous	Exon 4 of 7	ENSP00000538402.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27231 AN: 151882 Hom.: 2752 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.180 AC: 44895 AN: 249630 AF XY: 0.168

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0445

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.140 AC: 204133 AN: 1455192 Hom.: 17022 Cov.: 34 AF XY: 0.138 AC XY: 100060 AN XY: 724080

African (AFR) AF: 0.224 AC: 7443 AN: 33170

American (AMR) AF: 0.381 AC: 16798 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3752 AN: 25924

East Asian (EAS) AF: 0.0605 AC: 2388 AN: 39500

South Asian (SAS) AF: 0.123 AC: 10539 AN: 85792

European-Finnish (FIN) AF: 0.245 AC: 13048 AN: 53156

Middle Eastern (MID) AF: 0.152 AC: 871 AN: 5720

European-Non Finnish (NFE) AF: 0.127 AC: 140763 AN: 1107748

Other (OTH) AF: 0.142 AC: 8531 AN: 60068

GnomAD4 genome AF: 0.179 AC: 27265 AN: 152002 Hom.: 2757 Cov.: 32 AF XY: 0.185 AC XY: 13768 AN XY: 74284

African (AFR) AF: 0.223 AC: 9230 AN: 41428

American (AMR) AF: 0.281 AC: 4290 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3470

East Asian (EAS) AF: 0.0472 AC: 244 AN: 5174

South Asian (SAS) AF: 0.124 AC: 597 AN: 4816

European-Finnish (FIN) AF: 0.246 AC: 2600 AN: 10552

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9212 AN: 67984

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.137 Hom.: 840

Bravo AF: 0.187

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.62
DANN	Benign	0.22
PhyloP100		-0.10
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: rs4348159; hg19: chr4-69972952; COSMIC: COSV59441983;