4-69075473-C-T

Variant names:

• chr4-69075473-C-T
• rs7677996
• NM_001349568.2:c.-158-13999C>T

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-158-13999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,790 control chromosomes in the GnomAD database, including 15,574 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 0.43 (15574 hom., cov: 32)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001349568.2	c.-158-13999C>T		intron_variant	Intron 1 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-158-13999C>T		intron_variant	Intron 1 of 5	2		ENSP00000426206.1
UGT2B7	ENST00000509763.1	n.128-13999C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65179 AN: 151672 Hom.: 15548 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.430 AC: 65256 AN: 151790 Hom.: 15574 Cov.: 32 AF XY: 0.430 AC XY: 31856 AN XY: 74132

African (AFR) AF: 0.638 AC: 26413 AN: 41390

American (AMR) AF: 0.373 AC: 5683 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2930 AN: 5148

South Asian (SAS) AF: 0.410 AC: 1972 AN: 4806

European-Finnish (FIN) AF: 0.325 AC: 3414 AN: 10504

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22250 AN: 67936

Other (OTH) AF: 0.422 AC: 890 AN: 2110

Alfa AF: 0.354 Hom.: 5782

Bravo AF: 0.442

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.63
PhyloP100		-0.0080

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: rs7677996; hg19: chr4-69941191;