chr4-69112350-G-A

Position:

• chr4-69112350-G-A

Variant summary

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

The NM_001074.4(UGT2B7):​c.1311-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,428,130 control chromosomes in the GnomAD database, including 184,918 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 (27550 hom., cov: 32)
  • Exomes 𝑓: 0.49 (157368 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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]

UGT2B7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1311-107G>A		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1091-107G>A		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.564-107G>A		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1311-107G>A		intron_variant		1	NM_001074.4	ENSP00000304811.7
UGT2B7	ENST00000508661.5	c.1091-107G>A		intron_variant		2		ENSP00000427659.1
UGT2B7	ENST00000622664.1	c.1003-107G>A		intron_variant		5		ENSP00000483172.1
UGT2B7	ENST00000509763.1	n.629-107G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89317 AN: 151828 Hom.: 27502 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.490 AC: 625238 AN: 1276184 Hom.: 157368 AF XY: 0.491 AC XY: 307657 AN XY: 627184

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.589 AC: 89421 AN: 151946 Hom.: 27550 Cov.: 32 AF XY: 0.597 AC XY: 44313 AN XY: 74276

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.602

Alfa AF: 0.524 Hom.: 2739

Bravo AF: 0.603

Asia WGS AF: 0.642 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7658752; hg19: chr4-69978068;