rs12642938

chr4-69110499-T-C

Variant summary

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

The NM_001074.4(UGT2B7):c.1311-1958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,860 control chromosomes in the GnomAD database, including 27,876 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 (27876 hom., cov: 31)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.1311-1958T>C		intron_variant		ENST00000305231.12
UGT2B7	NM_001330719.2	c.1091-1958T>C		intron_variant
UGT2B7	NM_001349568.2	c.564-1958T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1311-1958T>C		intron_variant		1	NM_001074.4	P1
UGT2B7	ENST00000508661.5	c.1091-1958T>C		intron_variant		2
UGT2B7	ENST00000622664.1	c.1003-1958T>C		intron_variant		5
UGT2B7	ENST00000509763.1	n.629-1958T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89606 AN: 151742 Hom.: 27827 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.591 AC: 89711 AN: 151860 Hom.: 27876 Cov.: 31 AF XY: 0.598 AC XY: 44424 AN XY: 74236

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.600

Alfa AF: 0.524 Hom.: 2756

Bravo AF: 0.607

Asia WGS AF: 0.638 AC: 2213 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.3
Dann	Benign	0.40

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: rs12642938; hg19: chr4-69976217;