rs7435335

Variant names:

• chr4-69105617-G-A
• rs7435335
• NM_001074.4:c.1003-1558G>A

Variant summary

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

The NM_001074.4(UGT2B7):​c.1003-1558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,038 control chromosomes in the GnomAD database, including 2,937 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 0.18 (2937 hom., cov: 33)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.1003-1558G>A		intron_variant	Intron 3 of 5	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.1003-1558G>A		intron_variant	Intron 3 of 4		NP_001317648.1
UGT2B7	NM_001349568.2	c.256-1558G>A		intron_variant	Intron 4 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1003-1558G>A		intron_variant	Intron 3 of 5	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27933 AN: 151920 Hom.: 2934 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.184 AC: 27964 AN: 152038 Hom.: 2937 Cov.: 33 AF XY: 0.190 AC XY: 14097 AN XY: 74314

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.195

Alfa AF: 0.144 Hom.: 2931

Bravo AF: 0.192

Asia WGS AF: 0.121 AC: 418 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.33

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: rs7435335; hg19: chr4-69971335;