rs7441774

Positions:

• chr4-69098836-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.870+148G>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 1,336,300 control chromosomes in the GnomAD database, including 173,141 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 0.58 (26275 hom., cov: 32)
  • Exomes 𝑓: 0.49 (146866 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.870+148G>A		intron_variant		ENST00000305231.12
UGT2B7	NM_001330719.2	c.870+148G>A		intron_variant
UGT2B7	NM_001349568.2	c.123+148G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.870+148G>A		intron_variant		1	NM_001074.4	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87494 AN: 151626 Hom.: 26229 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.490 AC: 580846 AN: 1184556 Hom.: 146866 AF XY: 0.492 AC XY: 290808 AN XY: 591290

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.560

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.577 AC: 87595 AN: 151744 Hom.: 26275 Cov.: 32 AF XY: 0.586 AC XY: 43458 AN XY: 74156

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.588

Alfa AF: 0.502 Hom.: 19303

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.38

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: rs7441774; hg19: chr4-69964554; COSMIC: COSV59443094;