chr4-69099141-G-C

Variant names:

• chr4-69099141-G-C
• rs7434332
• NM_001074.4:c.870+453G>C

Variant summary

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

The NM_001074.4(UGT2B7):​c.870+453G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,152 control chromosomes in the GnomAD database, including 26,197 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 (26197 hom., cov: 29)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 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.870+453G>C		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.870+453G>C		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.123+453G>C		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.870+453G>C		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.870+453G>C		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.870+453G>C		intron	N/A	ENSP00000483172.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87234 AN: 151030 Hom.: 26150 Cov.: 29

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.578 AC: 87337 AN: 151152 Hom.: 26197 Cov.: 29 AF XY: 0.587 AC XY: 43334 AN XY: 73816

African (AFR) AF: 0.713 AC: 29434 AN: 41260

American (AMR) AF: 0.660 AC: 10020 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1773 AN: 3464

East Asian (EAS) AF: 0.702 AC: 3600 AN: 5126

South Asian (SAS) AF: 0.606 AC: 2911 AN: 4802

European-Finnish (FIN) AF: 0.580 AC: 6013 AN: 10364

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

European-Non Finnish (NFE) AF: 0.469 AC: 31740 AN: 67672

Other (OTH) AF: 0.588 AC: 1231 AN: 2092

Alfa AF: 0.339 Hom.: 783

Bravo AF: 0.590

Asia WGS AF: 0.656 AC: 2277 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.38
PhyloP100		-0.21
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: rs7434332; hg19: chr4-69964859;