4-69107949-C-G

Position:

• chr4-69107949-C-G

Variant summary

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

The NM_001074.4(UGT2B7):​c.1091-154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,032 control chromosomes in the GnomAD database, including 27,892 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 0.59 (27892 hom., cov: 32)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1091-154C>G		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1090+687C>G		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.344-154C>G		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1091-154C>G		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89688 AN: 151914 Hom.: 27843 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.591 AC: 89793 AN: 152032 Hom.: 27892 Cov.: 32 AF XY: 0.598 AC XY: 44459 AN XY: 74296

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.599

Alfa AF: 0.379 Hom.: 1018

Bravo AF: 0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4588522; hg19: chr4-69973667; COSMIC: COSV59446101;