4-69107807-C-A

Variant names:

• chr4-69107807-C-A
• rs4521414
• NM_001074.4:c.1091-296C>A

Variant summary

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

The NM_001074.4(UGT2B7):​c.1091-296C>A 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 151,742 control chromosomes in the GnomAD database, including 27,834 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 (27834 hom., cov: 30)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001074.4	MANE Select	c.1091-296C>A		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.1090+545C>A		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.344-296C>A		intron	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.1091-296C>A		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.1090+545C>A		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.1003-4650C>A		intron	N/A	ENSP00000483172.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89509 AN: 151624 Hom.: 27785 Cov.: 30

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.591 AC: 89614 AN: 151742 Hom.: 27834 Cov.: 30 AF XY: 0.598 AC XY: 44362 AN XY: 74148

African (AFR) AF: 0.766 AC: 31683 AN: 41356

American (AMR) AF: 0.665 AC: 10130 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3468

East Asian (EAS) AF: 0.702 AC: 3619 AN: 5154

South Asian (SAS) AF: 0.554 AC: 2655 AN: 4790

European-Finnish (FIN) AF: 0.574 AC: 6038 AN: 10518

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31842 AN: 67916

Other (OTH) AF: 0.600 AC: 1259 AN: 2100

Alfa AF: 0.517 Hom.: 27583

Bravo AF: 0.607

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.21
PhyloP100		-0.012
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: rs4521414; hg19: chr4-69973525;