4-69096194-A-G

Position:

• chr4-69096194-A-G

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-2346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,992 control chromosomes in the GnomAD database, including 26,306 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 0.58 (26306 hom., cov: 33)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001349568.2	c.-26-2346A>G		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-26-2346A>G		intron_variant		2		ENSP00000426206
UGT2B7	ENST00000509763.1	n.260-2346A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87598 AN: 151874 Hom.: 26260 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87699 AN: 151992 Hom.: 26306 Cov.: 33 AF XY: 0.586 AC XY: 43510 AN XY: 74284

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.589

Alfa AF: 0.499 Hom.: 26940

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.42

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: rs7662029; hg19: chr4-69961912;