rs9658668

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001275.4(CHGA):​c.1163C>T​(p.Pro388Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,610,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

CHGA
NM_001275.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.191

Publications

7 publications found
Variant links:
Genes affected
CHGA (HGNC:1929): (chromogranin A) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005293399).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHGANM_001275.4 linkc.1163C>T p.Pro388Leu missense_variant Exon 7 of 8 ENST00000216492.10 NP_001266.1 P10645Q86T07
CHGANM_001301690.2 linkc.710C>T p.Pro237Leu missense_variant Exon 6 of 7 NP_001288619.1 P10645G5E968Q86T07
CHGAXM_011536370.3 linkc.1163C>T p.Pro388Leu missense_variant Exon 8 of 9 XP_011534672.1 P10645

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHGAENST00000216492.10 linkc.1163C>T p.Pro388Leu missense_variant Exon 7 of 8 1 NM_001275.4 ENSP00000216492.5 P10645
CHGAENST00000334654.4 linkc.710C>T p.Pro237Leu missense_variant Exon 6 of 7 1 ENSP00000334023.4 G5E968
CHGAENST00000556876.1 linkn.381C>T non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00118
AC:
179
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00403
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000386
AC:
92
AN:
238524
AF XY:
0.000398
show subpopulations
Gnomad AFR exome
AF:
0.00423
Gnomad AMR exome
AF:
0.000147
Gnomad ASJ exome
AF:
0.00124
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000848
Gnomad OTH exome
AF:
0.000520
GnomAD4 exome
AF:
0.000214
AC:
312
AN:
1458666
Hom.:
1
Cov.:
31
AF XY:
0.000197
AC XY:
143
AN XY:
725432
show subpopulations
African (AFR)
AF:
0.00439
AC:
147
AN:
33464
American (AMR)
AF:
0.000269
AC:
12
AN:
44608
Ashkenazi Jewish (ASJ)
AF:
0.00123
AC:
32
AN:
26032
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39666
South Asian (SAS)
AF:
0.0000234
AC:
2
AN:
85642
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51906
Middle Eastern (MID)
AF:
0.000175
AC:
1
AN:
5708
European-Non Finnish (NFE)
AF:
0.0000720
AC:
80
AN:
1111458
Other (OTH)
AF:
0.000631
AC:
38
AN:
60182
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
21
42
62
83
104
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00120
AC:
183
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.00114
AC XY:
85
AN XY:
74446
show subpopulations
African (AFR)
AF:
0.00412
AC:
171
AN:
41548
American (AMR)
AF:
0.000261
AC:
4
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00115
AC:
4
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000588
AC:
4
AN:
67988
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
12
25
37
50
62
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000536
Hom.:
0
Bravo
AF:
0.00120
ESP6500AA
AF:
0.00320
AC:
14
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.000380
AC:
46
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
7.3
DANN
Benign
0.91
DEOGEN2
Benign
0.20
T;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.051
N
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.0053
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.020
N;.
PhyloP100
0.19
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Benign
0.040
Sift
Benign
0.25
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.0050
B;B
Vest4
0.092
MVP
0.34
MPC
0.20
ClinPred
0.0085
T
GERP RS
0.27
Varity_R
0.048
gMVP
0.065
Mutation Taster
=96/4
polymorphism

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

Publications

Other links and lift over

dbSNP: rs9658668; hg19: chr14-93399069; API