4-69096360-T-A

Variant names:

• chr4-69096360-T-A
• rs7668258
• NM_001349568.2:c.-26-2180T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349568.2(UGT2B7):​c.-26-2180T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 95 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349568.2. 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_001349568.2		c.-26-2180T>A		intron	N/A	NP_001336497.1
	UGT2B7	NM_001074.4	MANE Select	c.-161T>A		upstream_gene	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.-161T>A		upstream_gene	N/A	NP_001317648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000502942.5	TSL:2	c.-26-2180T>A		intron	N/A	ENSP00000426206.1
	UGT2B7	ENST00000509763.1	TSL:5	n.260-2180T>A		intron	N/A
	ENSG00000299782	ENST00000766360.1		n.443-871A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 980768 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 492934

African (AFR) AF: 0.00 AC: 0 AN: 22158

American (AMR) AF: 0.00 AC: 0 AN: 20764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17258

East Asian (EAS) AF: 0.00 AC: 0 AN: 34366

South Asian (SAS) AF: 0.00 AC: 0 AN: 59118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 740156

Other (OTH) AF: 0.00 AC: 0 AN: 43578

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.094
DANN	Benign	0.50
PhyloP100		-1.7
PromoterAI		-0.023	Neutral

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: rs7668258; hg19: chr4-69962078;