rs11940220

Positions:

• chr4-69095222-T-C
• chr4-69095222-T-G

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-3318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,500 control chromosomes in the GnomAD database, including 26,047 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 (26047 hom., cov: 33)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001349568.2	c.-26-3318T>C		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-26-3318T>C		intron_variant		2		ENSP00000426206
UGT2B7	ENST00000509763.1	n.260-3318T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87083 AN: 151382 Hom.: 26001 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.575 AC: 87184 AN: 151500 Hom.: 26047 Cov.: 33 AF XY: 0.584 AC XY: 43203 AN XY: 73960

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.588

Alfa AF: 0.373 Hom.: 982

Bravo AF: 0.590

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.24

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: rs11940220; hg19: chr4-69960940;