chr4-69108008-G-A

Variant names:

• chr4-69108008-G-A
• rs10022440
• NM_001074.4:c.1091-95G>A

Variant summary

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

The NM_001074.4(UGT2B7):​c.1091-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,471,668 control chromosomes in the GnomAD database, including 3,767 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 0.062 (349 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3418 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. 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.1091-95G>A		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.1090+746G>A		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.344-95G>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.1091-95G>A		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000868341.1		c.1187-95G>A		intron	N/A	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.1091-95G>A		intron	N/A	ENSP00000538402.1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9383 AN: 152084 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0682 AC: 89984 AN: 1319466 Hom.: 3418 AF XY: 0.0668 AC XY: 44262 AN XY: 662162

African (AFR) AF: 0.0513 AC: 1496 AN: 29176

American (AMR) AF: 0.0436 AC: 1618 AN: 37094

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 1672 AN: 23698

East Asian (EAS) AF: 0.000128 AC: 5 AN: 38970

South Asian (SAS) AF: 0.0267 AC: 2114 AN: 79114

European-Finnish (FIN) AF: 0.0472 AC: 2458 AN: 52078

Middle Eastern (MID) AF: 0.0836 AC: 397 AN: 4746

European-Non Finnish (NFE) AF: 0.0766 AC: 76604 AN: 999470

Other (OTH) AF: 0.0657 AC: 3620 AN: 55120

GnomAD4 genome AF: 0.0617 AC: 9386 AN: 152202 Hom.: 349 Cov.: 32 AF XY: 0.0597 AC XY: 4442 AN XY: 74408

African (AFR) AF: 0.0514 AC: 2135 AN: 41520

American (AMR) AF: 0.0623 AC: 952 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4824

European-Finnish (FIN) AF: 0.0480 AC: 509 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5201 AN: 67998

Other (OTH) AF: 0.0677 AC: 143 AN: 2112

Alfa AF: 0.0639 Hom.: 155

Bravo AF: 0.0625

Asia WGS AF: 0.0160 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.59
PhyloP100		-0.38
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: rs10022440; hg19: chr4-69973726;