rs10022440

Positions:

• chr4-69108008-G-A

Variant summary

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

The NM_001074.4(UGT2B7):​c.1091-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,471,668 control chromosomes in the GnomAD database, including 3,767 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 0.062 (349 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3418 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1091-95G>A		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1090+746G>A		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.344-95G>A		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1091-95G>A		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9383 AN: 152084 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0682 AC: 89984 AN: 1319466 Hom.: 3418 AF XY: 0.0668 AC XY: 44262 AN XY: 662162

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.0436

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0472

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0657

GnomAD4 genome AF: 0.0617 AC: 9386 AN: 152202 Hom.: 349 Cov.: 32 AF XY: 0.0597 AC XY: 4442 AN XY: 74408

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.0480

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0725 Hom.: 93

Bravo AF: 0.0625

Asia WGS AF: 0.0160 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.59

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: rs10022440; hg19: chr4-69973726;