rs62298861

Positions:

• chr4-69098226-A-G
• chr4-69098226-A-T

Variant summary

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

The NM_001074.4(UGT2B7):​c.722-314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,826 control chromosomes in the GnomAD database, including 3,171 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 0.19 (3171 hom., cov: 32)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.722-314A>G		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.722-314A>G		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.-26-314A>G		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.722-314A>G		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28838 AN: 151706 Hom.: 3168 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.190 AC: 28876 AN: 151826 Hom.: 3171 Cov.: 32 AF XY: 0.196 AC XY: 14520 AN XY: 74206

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.197

Alfa AF: 0.165 Hom.: 330

Bravo AF: 0.200

Asia WGS AF: 0.123 AC: 425 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.26

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: rs62298861; hg19: chr4-69963944;