chr7-99715770-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000765.5(CYP3A7):​c.658G>A​(p.Val220Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CYP3A7
NM_000765.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.75
Variant links:
Genes affected
CYP3A7 (HGNC:2640): (cytochrome P450 family 3 subfamily A member 7) This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the synthesis of cholesterol, steroids and other lipids. This enzyme hydroxylates testosterone and dehydroepiandrosterone 3-sulphate, which is involved in the formation of estriol during pregnancy. This gene is part of a cluster of related genes on chromosome 7q21.1. Naturally-occurring readthrough transcription occurs between this gene and the downstream CYP3A51P pseudogene and is represented by GeneID:100861540. [provided by RefSeq, Jan 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.061219364).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP3A7NM_000765.5 linkuse as main transcriptc.658G>A p.Val220Ile missense_variant 7/13 ENST00000336374.4
CYP3A7-CYP3A51PNM_001256497.3 linkuse as main transcriptc.658G>A p.Val220Ile missense_variant 7/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP3A7ENST00000336374.4 linkuse as main transcriptc.658G>A p.Val220Ile missense_variant 7/131 NM_000765.5 P1P24462-1
CYP3A7ENST00000477357.5 linkuse as main transcriptn.997G>A non_coding_transcript_exon_variant 4/102
CYP3A7ENST00000498080.1 linkuse as main transcriptn.226G>A non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251210
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135772
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461476
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 05, 2022The c.658G>A (p.V220I) alteration is located in exon 7 (coding exon 7) of the CYP3A7 gene. This alteration results from a G to A substitution at nucleotide position 658, causing the valine (V) at amino acid position 220 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.0010
DANN
Benign
0.48
DEOGEN2
Benign
0.095
.;T;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.0094
N
LIST_S2
Benign
0.44
T;T;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.061
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
.;N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.79
.;N;.
REVEL
Benign
0.12
Sift
Benign
0.54
.;T;.
Sift4G
Benign
0.76
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.12
MVP
0.15
MPC
0.099
ClinPred
0.039
T
GERP RS
-8.2
Varity_R
0.016
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149501739; hg19: chr7-99313393; API