rs2687116
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
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
NM_017460.6 intron
Scores
2
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 3Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP3A4 | ENST00000651514.1 | c.670+34G>T | intron_variant | Intron 7 of 12 | NM_017460.6 | ENSP00000498939.1 | ||||
CYP3A4 | ENST00000336411.7 | c.670+34G>T | intron_variant | Intron 7 of 13 | 1 | ENSP00000337915.3 | ||||
CYP3A4 | ENST00000652018.1 | c.523+34G>T | intron_variant | Intron 5 of 10 | ENSP00000498733.1 | |||||
CYP3A4 | ENST00000354593.6 | c.220+34G>T | intron_variant | Intron 2 of 7 | 5 | ENSP00000346607.2 |
Frequencies
GnomAD3 genomes AF: 0.799 AC: 121423AN: 151954Hom.: 53438 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
121423
AN:
151954
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.921 AC: 228420AN: 248068 AF XY: 0.933 show subpopulations
GnomAD2 exomes
AF:
AC:
228420
AN:
248068
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.949 AC: 1372018AN: 1445060Hom.: 657644 Cov.: 29 AF XY: 0.952 AC XY: 685206AN XY: 719872 show subpopulations
GnomAD4 exome
AF:
AC:
1372018
AN:
1445060
Hom.:
Cov.:
29
AF XY:
AC XY:
685206
AN XY:
719872
show subpopulations
African (AFR)
AF:
AC:
12119
AN:
32992
American (AMR)
AF:
AC:
40466
AN:
44234
Ashkenazi Jewish (ASJ)
AF:
AC:
24666
AN:
25950
East Asian (EAS)
AF:
AC:
39477
AN:
39500
South Asian (SAS)
AF:
AC:
82325
AN:
85440
European-Finnish (FIN)
AF:
AC:
51153
AN:
53348
Middle Eastern (MID)
AF:
AC:
5394
AN:
5708
European-Non Finnish (NFE)
AF:
AC:
1060997
AN:
1098146
Other (OTH)
AF:
AC:
55421
AN:
59742
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
2812
5625
8437
11250
14062
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
21188
42376
63564
84752
105940
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.799 AC: 121456AN: 152074Hom.: 53443 Cov.: 32 AF XY: 0.806 AC XY: 59912AN XY: 74348 show subpopulations
GnomAD4 genome
AF:
AC:
121456
AN:
152074
Hom.:
Cov.:
32
AF XY:
AC XY:
59912
AN XY:
74348
show subpopulations
African (AFR)
AF:
AC:
16097
AN:
41376
American (AMR)
AF:
AC:
13561
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
3293
AN:
3470
East Asian (EAS)
AF:
AC:
5165
AN:
5178
South Asian (SAS)
AF:
AC:
4633
AN:
4820
European-Finnish (FIN)
AF:
AC:
10229
AN:
10614
Middle Eastern (MID)
AF:
AC:
271
AN:
294
European-Non Finnish (NFE)
AF:
AC:
65594
AN:
68024
Other (OTH)
AF:
AC:
1783
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
764
1528
2291
3055
3819
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
830
1660
2490
3320
4150
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3251
AN:
3476
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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