4-69051355-C-T

Variant names:

• chr4-69051355-C-T
• rs4377650
• ENST00000766642.1:n.52-4236G>A

Variant summary

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

The ENST00000766642.1(ENSG00000299813):​n.52-4236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,082 control chromosomes in the GnomAD database, including 17,806 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 0.46 (17799 hom., cov: 32)
  • Exomes 𝑓: 0.44 (7 hom.)
• Consequence: ENSG00000299813 ENST00000766642.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 3 publications found

Genes affected

ENSG00000299813 (HGNC:58801):

LOC105377265 (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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000766642.1. 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_001349568.2		c.-406C>T		upstream_gene	N/A	NP_001336497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000299813	ENST00000766642.1		n.52-4236G>A		intron	N/A
	UGT2B7	ENST00000502942.5	TSL:2	c.-406C>T		upstream_gene	N/A	ENSP00000426206.1
	UGT2B7	ENST00000509763.1	TSL:5	n.-121C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70337 AN: 151910 Hom.: 17775 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.442 AC: 23 AN: 52 Hom.: 7 Cov.: 0 AF XY: 0.447 AC XY: 17 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.523 AC: 23 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.463 AC: 70405 AN: 152030 Hom.: 17799 Cov.: 32 AF XY: 0.463 AC XY: 34389 AN XY: 74288

African (AFR) AF: 0.665 AC: 27574 AN: 41456

American (AMR) AF: 0.426 AC: 6510 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1780 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2973 AN: 5156

South Asian (SAS) AF: 0.429 AC: 2066 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3792 AN: 10578

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24266 AN: 67958

Other (OTH) AF: 0.468 AC: 990 AN: 2116

Alfa AF: 0.444 Hom.: 2456

Bravo AF: 0.477

Asia WGS AF: 0.479 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		-2.1
PromoterAI		-0.047	Neutral

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: rs4377650; hg19: chr4-69917073;