rs4377650

Positions:

• chr4-69051355-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_001741714.2(LOC105377265):​n.3048-1219G>A variant causes a intron, non coding transcript 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: LOC105377265 XR_001741714.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

Genes affected

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105377265	XR_001741714.2	n.3048-1219G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000502942.5			upstream_gene_variant		2

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

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.468

Alfa AF: 0.435 Hom.: 2273

Bravo AF: 0.477

Asia WGS AF: 0.479 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs4377650; hg19: chr4-69917073;