rs7801671

Variant names:

• chr7-99779283-C-A
• rs7801671
• NM_017460.6:c.165+709G>T

Variant summary

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

The NM_017460.6(CYP3A4):​c.165+709G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 151,866 control chromosomes in the GnomAD database, including 856 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 0.058 (856 hom., cov: 32)
• Consequence: CYP3A4 NM_017460.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 6 publications found

Genes affected

CYP3A4 (HGNC:2637): (cytochrome P450 family 3 subfamily A member 4) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2020]

CYP3A4 Gene-Disease associations (from GenCC):

• vitamin D-dependent rickets, type 3

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A4	NM_017460.6	c.165+709G>T		intron_variant	Intron 2 of 12	ENST00000651514.1	NP_059488.2
CYP3A4	NM_001202855.3	c.165+709G>T		intron_variant	Intron 2 of 12		NP_001189784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A4	ENST00000651514.1	c.165+709G>T		intron_variant	Intron 2 of 12		NM_017460.6	ENSP00000498939.1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8749 AN: 151756 Hom.: 853 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0578 AC: 8781 AN: 151866 Hom.: 856 Cov.: 32 AF XY: 0.0560 AC XY: 4153 AN XY: 74194

African (AFR) AF: 0.199 AC: 8234 AN: 41390

American (AMR) AF: 0.0260 AC: 396 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00250 AC: 12 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10476

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67980

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0237 Hom.: 772

Bravo AF: 0.0663

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		0.23
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: rs7801671; hg19: chr7-99376906;