rs7668282

Positions:

• chr4-69096396-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349568.2(UGT2B7):​c.-26-2144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,439,516 control chromosomes in the GnomAD database, including 922 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 0.025 (114 hom., cov: 32)
  • Exomes 𝑓: 0.016 (808 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001349568.2	c.-26-2144T>C		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-26-2144T>C		intron_variant		2		ENSP00000426206
UGT2B7	ENST00000509763.1	n.260-2144T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3736 AN: 152180 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0816

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00692

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0162 AC: 20867 AN: 1287218 Hom.: 808 AF XY: 0.0187 AC XY: 11945 AN XY: 640448

Gnomad4 AFR exome AF: 0.0436

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.00386

Gnomad4 EAS exome AF: 0.0830

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.00386

Gnomad4 NFE exome AF: 0.00620

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0246 AC: 3741 AN: 152298 Hom.: 114 Cov.: 32 AF XY: 0.0274 AC XY: 2037 AN XY: 74468

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0816

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00692

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0107 Hom.: 20

Bravo AF: 0.0250

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs7668282; hg19: chr4-69962114;