NM_001074.4:c.722-49A>G

Variant names:

• chr4-69098491-A-G
• rs7438244
• NM_001074.4:c.722-49A>G

Variant summary

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

The NM_001074.4(UGT2B7):​c.722-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,567,062 control chromosomes in the GnomAD database, including 200,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (26128 hom., cov: 30)
  • Exomes 𝑓: 0.49 (174050 hom.)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.303
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 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.722-49A>G		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.722-49A>G		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.-26-49A>G		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.722-49A>G		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.722-49A>G		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.722-49A>G		intron	N/A	ENSP00000483172.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87059 AN: 151076 Hom.: 26083 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.587

GnomAD2 exomes AF: 0.549 AC: 116698 AN: 212428 AF XY: 0.541

Gnomad AFR exome AF: 0.713

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.698

Gnomad FIN exome AF: 0.579

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.489 AC: 692468 AN: 1415874 Hom.: 174050 Cov.: 30 AF XY: 0.490 AC XY: 344857 AN XY: 703380

African (AFR) AF: 0.714 AC: 21712 AN: 30426

American (AMR) AF: 0.689 AC: 21386 AN: 31028

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 12126 AN: 24026

East Asian (EAS) AF: 0.703 AC: 27536 AN: 39192

South Asian (SAS) AF: 0.561 AC: 43141 AN: 76868

European-Finnish (FIN) AF: 0.577 AC: 30319 AN: 52504

Middle Eastern (MID) AF: 0.525 AC: 2914 AN: 5550

European-Non Finnish (NFE) AF: 0.458 AC: 503353 AN: 1097916

Other (OTH) AF: 0.514 AC: 29981 AN: 58364

GnomAD4 genome AF: 0.576 AC: 87156 AN: 151188 Hom.: 26128 Cov.: 30 AF XY: 0.585 AC XY: 43161 AN XY: 73756

African (AFR) AF: 0.713 AC: 29418 AN: 41268

American (AMR) AF: 0.660 AC: 9981 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1772 AN: 3464

East Asian (EAS) AF: 0.701 AC: 3614 AN: 5156

South Asian (SAS) AF: 0.604 AC: 2905 AN: 4806

European-Finnish (FIN) AF: 0.570 AC: 5881 AN: 10310

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.468 AC: 31739 AN: 67760

Other (OTH) AF: 0.587 AC: 1230 AN: 2094

Alfa AF: 0.512 Hom.: 6250

Bravo AF: 0.590

Asia WGS AF: 0.656 AC: 2277 AN: 3474

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-0.30
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: rs7438244; hg19: chr4-69964209; COSMIC: COSV59443076;