4-69105617-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000305231.12(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 ENST00000305231.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 13 publications found

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]

ENSG00000299782 (HGNC:58802):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305231.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001074.4	MANE Select	c.1003-1558G>A		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.1003-1558G>A		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.256-1558G>A		intron	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.1003-1558G>A		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.1003-1558G>A		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.1002+2679G>A		intron	N/A	ENSP00000483172.1

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

African (AFR) AF: 0.239 AC: 9896 AN: 41484

American (AMR) AF: 0.283 AC: 4311 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.0477 AC: 247 AN: 5182

South Asian (SAS) AF: 0.124 AC: 597 AN: 4826

European-Finnish (FIN) AF: 0.246 AC: 2596 AN: 10544

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9218 AN: 67964

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.148 Hom.: 7061

Bravo AF: 0.192

Asia WGS AF: 0.121 AC: 418 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7435335; hg19: chr4-69971335;