rs2687116

Variant names:

• chr7-99768320-C-A
• rs2687116
• NM_017460.6:c.670+34G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-99768320-C-A
• chr7-99768320-C-G
• chr7-99768320-C-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.670+34G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 1,597,134 control chromosomes in the GnomAD database, including 711,087 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 0.80 (53443 hom., cov: 32)
  • Exomes 𝑓: 0.95 (657644 hom.)
• Consequence: CYP3A4 NM_017460.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 29 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017460.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A4	NM_017460.6	MANE Select	c.670+34G>T		intron	N/A	NP_059488.2
	CYP3A4	NM_001202855.3		c.670+34G>T		intron	N/A	NP_001189784.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A4	ENST00000651514.1	MANE Select	c.670+34G>T		intron	N/A	ENSP00000498939.1	P08684
	CYP3A4	ENST00000336411.7	TSL:1	c.670+34G>T		intron	N/A	ENSP00000337915.3	A0A499FJM4
	CYP3A4	ENST00000859201.1		c.670+34G>T		intron	N/A	ENSP00000529260.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121423 AN: 151954 Hom.: 53438 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.847

GnomAD2 exomes AF: 0.921 AC: 228420 AN: 248068 AF XY: 0.933

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.918

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.960

Gnomad NFE exome AF: 0.964

Gnomad OTH exome AF: 0.942

GnomAD4 exome AF: 0.949 AC: 1372018 AN: 1445060 Hom.: 657644 Cov.: 29 AF XY: 0.952 AC XY: 685206 AN XY: 719872

African (AFR) AF: 0.367 AC: 12119 AN: 32992

American (AMR) AF: 0.915 AC: 40466 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 24666 AN: 25950

East Asian (EAS) AF: 0.999 AC: 39477 AN: 39500

South Asian (SAS) AF: 0.964 AC: 82325 AN: 85440

European-Finnish (FIN) AF: 0.959 AC: 51153 AN: 53348

Middle Eastern (MID) AF: 0.945 AC: 5394 AN: 5708

European-Non Finnish (NFE) AF: 0.966 AC: 1060997 AN: 1098146

Other (OTH) AF: 0.928 AC: 55421 AN: 59742

GnomAD4 genome AF: 0.799 AC: 121456 AN: 152074 Hom.: 53443 Cov.: 32 AF XY: 0.806 AC XY: 59912 AN XY: 74348

African (AFR) AF: 0.389 AC: 16097 AN: 41376

American (AMR) AF: 0.887 AC: 13561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3293 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5165 AN: 5178

South Asian (SAS) AF: 0.961 AC: 4633 AN: 4820

European-Finnish (FIN) AF: 0.964 AC: 10229 AN: 10614

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65594 AN: 68024

Other (OTH) AF: 0.847 AC: 1783 AN: 2106

Alfa AF: 0.793 Hom.: 31853

Bravo AF: 0.773

Asia WGS AF: 0.935 AC: 3251 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.13
PhyloP100		-2.0
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: rs2687116; hg19: chr7-99365943;