rs587776861
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000513720.5(AFP):n.147-1060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 514,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
AFP
ENST00000513720.5 intron
ENST00000513720.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.980
Publications
2 publications found
Genes affected
AFP (HGNC:317): (alpha fetoprotein) This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]
AFP Gene-Disease associations (from GenCC):
- hereditary persistence of alpha-fetoproteinInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- congenital deficiency in alpha-fetoproteinInheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000513720.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| AFP | NM_001134.3 | MANE Select | c.-163G>A | upstream_gene | N/A | NP_001125.1 | P02771 | ||
| AFP | NM_001354717.2 | c.-495G>A | upstream_gene | N/A | NP_001341646.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AFP | ENST00000513720.5 | TSL:1 | n.147-1060G>A | intron | N/A | ||||
| AFP | ENST00000515675.1 | TSL:1 | n.267-1060G>A | intron | N/A | ||||
| AFP | ENST00000395792.7 | TSL:1 MANE Select | c.-163G>A | upstream_gene | N/A | ENSP00000379138.2 | P02771 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151718Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151718
Hom.:
Cov.:
33
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:
GnomAD4 exome AF: 0.00000276 AC: 1AN: 362886Hom.: 0 AF XY: 0.00000519 AC XY: 1AN XY: 192624 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
362886
Hom.:
AF XY:
AC XY:
1
AN XY:
192624
show subpopulations
African (AFR)
AF:
AC:
0
AN:
9622
American (AMR)
AF:
AC:
0
AN:
12442
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
11746
East Asian (EAS)
AF:
AC:
0
AN:
26500
South Asian (SAS)
AF:
AC:
1
AN:
27892
European-Finnish (FIN)
AF:
AC:
0
AN:
30848
Middle Eastern (MID)
AF:
AC:
0
AN:
1678
European-Non Finnish (NFE)
AF:
AC:
0
AN:
220756
Other (OTH)
AF:
AC:
0
AN:
21402
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome 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
GnomAD4 genome 0.00000659 AC: 1AN: 151718Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74088 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151718
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74088
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41314
American (AMR)
AF:
AC:
0
AN:
15220
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
1
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10524
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67874
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
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:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Affects
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
-
-
Alpha-fetoprotein, hereditary persistence of (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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