rs28375964

Variant names:

• chr4-69098070-C-T
• rs28375964
• NM_001074.4:c.722-470C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001074.4(UGT2B7):​c.722-470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,752 control chromosomes in the GnomAD database, including 31,192 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 0.63 (31192 hom., cov: 32)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.04
• Publications: 4 publications found

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]

ENSG00000299782 (HGNC:58802):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001074.4	MANE Select	c.722-470C>T		intron	N/A	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.722-470C>T		intron	N/A	NP_001317648.1	E9PBP8
	UGT2B7	NM_001349568.2		c.-26-470C>T		intron	N/A	NP_001336497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.722-470C>T		intron	N/A	ENSP00000304811.7	P16662
	UGT2B7	ENST00000868341.1		c.722-470C>T		intron	N/A	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.722-470C>T		intron	N/A	ENSP00000538402.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94874 AN: 151634 Hom.: 31147 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.626 AC: 94970 AN: 151752 Hom.: 31192 Cov.: 32 AF XY: 0.634 AC XY: 47038 AN XY: 74154

African (AFR) AF: 0.808 AC: 33502 AN: 41446

American (AMR) AF: 0.698 AC: 10620 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3468

East Asian (EAS) AF: 0.702 AC: 3629 AN: 5172

South Asian (SAS) AF: 0.613 AC: 2947 AN: 4810

European-Finnish (FIN) AF: 0.607 AC: 6402 AN: 10544

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33612 AN: 67792

Other (OTH) AF: 0.646 AC: 1362 AN: 2108

Alfa AF: 0.568 Hom.: 3374

Bravo AF: 0.643

Asia WGS AF: 0.666 AC: 2297 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0070
DANN	Benign	0.14
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28375964; hg19: chr4-69963788;