rs4422474

Positions:

• chr4-69051322-G-A
• chr4-69051322-G-C
• chr4-69051322-G-T

Variant summary

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

The XR_938851.2(LOC105377265):​n.316-1186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,102 control chromosomes in the GnomAD database, including 17,533 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 (17527 hom., cov: 32)
  • Exomes 𝑓: 0.30 (6 hom.)
• Consequence: LOC105377265 XR_938851.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377265	XR_001741714.2	n.3048-1186C>T		intron_variant
LOC105377265	XR_938851.2	n.316-1186C>T		intron_variant
LOC105377265	XR_938852.2	n.316-1294C>T		intron_variant
LOC105377265	XR_938854.2	n.298-1186C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-439G>A		upstream_gene_variant		2		ENSP00000426206.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69909 AN: 151904 Hom.: 17505 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.300 AC: 24 AN: 80 Hom.: 6 Cov.: 0 AF XY: 0.354 AC XY: 17 AN XY: 48

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.460 AC: 69975 AN: 152022 Hom.: 17527 Cov.: 32 AF XY: 0.460 AC XY: 34207 AN XY: 74288

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.465

Alfa AF: 0.388 Hom.: 1500

Bravo AF: 0.474

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.64

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: rs4422474; hg19: chr4-69917040;