rs6600893

Variant names:

• chr4-69113183-T-C
• rs6600893
• ENST00000766360.1:n.253-479A>G

Variant summary

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

The ENST00000766360.1(ENSG00000299782):​n.253-479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,072 control chromosomes in the GnomAD database, including 27,537 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 (27537 hom., cov: 33)
• Consequence: ENSG00000299782 ENST00000766360.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 14 publications found

Genes affected

ENSG00000299782 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.*447T>C		downstream_gene_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.*707T>C		downstream_gene_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.*447T>C		downstream_gene_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.*447T>C		downstream_gene_variant		1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89324 AN: 151954 Hom.: 27489 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.588 AC: 89428 AN: 152072 Hom.: 27537 Cov.: 33 AF XY: 0.596 AC XY: 44293 AN XY: 74328

African (AFR) AF: 0.751 AC: 31181 AN: 41506

American (AMR) AF: 0.667 AC: 10196 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3468

East Asian (EAS) AF: 0.704 AC: 3636 AN: 5166

South Asian (SAS) AF: 0.550 AC: 2647 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6067 AN: 10568

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32039 AN: 67938

Other (OTH) AF: 0.600 AC: 1267 AN: 2110

Alfa AF: 0.526 Hom.: 37130

Bravo AF: 0.603

Asia WGS AF: 0.635 AC: 2199 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.62
PhyloP100		-0.67

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: rs6600893; hg19: chr4-69978901;