chr5-76953678-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001882.4(CRHBP):c.159G>C(p.Pro53Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,608,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P53P) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
CRHBP
NM_001882.4 synonymous
NM_001882.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0990
Publications
4 publications found
Genes affected
CRHBP (HGNC:2356): (corticotropin releasing hormone binding protein) Corticotropin-releasing hormone is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRH concentrations in the human peripheral circulation are normally low, they increase throughout pregnancy and fall rapidly after parturition. Maternal plasma CRH probably originates from the placenta. Human plasma contains a CRH-binding protein which inactivates CRH and which may prevent inappropriate pituitary-adrenal stimulation in pregnancy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP7
Synonymous conserved (PhyloP=-0.099 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CRHBP | NM_001882.4 | c.159G>C | p.Pro53Pro | synonymous_variant | Exon 2 of 7 | ENST00000274368.9 | NP_001873.2 | |
| CRHBP | XR_948235.4 | n.249G>C | non_coding_transcript_exon_variant | Exon 2 of 8 | ||||
| CRHBP | XM_047416736.1 | c.-74G>C | 5_prime_UTR_variant | Exon 1 of 6 | XP_047272692.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CRHBP | ENST00000274368.9 | c.159G>C | p.Pro53Pro | synonymous_variant | Exon 2 of 7 | 1 | NM_001882.4 | ENSP00000274368.4 | ||
| CRHBP | ENST00000506501.1 | c.159G>C | p.Pro53Pro | synonymous_variant | Exon 2 of 5 | 1 | ENSP00000426097.1 | |||
| CRHBP | ENST00000512446.1 | n.262G>C | non_coding_transcript_exon_variant | Exon 1 of 4 | 2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000853 AC: 2AN: 234540 AF XY: 0.0000156 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
234540
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000686 AC: 10AN: 1456824Hom.: 0 Cov.: 31 AF XY: 0.00000828 AC XY: 6AN XY: 724210 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1456824
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
724210
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33392
American (AMR)
AF:
AC:
0
AN:
44226
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25992
East Asian (EAS)
AF:
AC:
0
AN:
39554
South Asian (SAS)
AF:
AC:
0
AN:
85206
European-Finnish (FIN)
AF:
AC:
0
AN:
52714
Middle Eastern (MID)
AF:
AC:
0
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1109932
Other (OTH)
AF:
AC:
0
AN:
60080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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4
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<30
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74332
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41442
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5154
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68046
Other (OTH)
AF:
AC:
0
AN:
2092
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
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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