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GeneBe

5-76953678-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001882.4(CRHBP):c.159G>A(p.Pro53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,609,112 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 33)
Exomes 𝑓: 0.0064 ( 53 hom. )

Consequence

CRHBP
NM_001882.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990
Variant links:
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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-76953678-G-A is Benign according to our data. Variant chr5-76953678-G-A is described in ClinVar as [Benign]. Clinvar id is 711390.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.099 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRHBPNM_001882.4 linkuse as main transcriptc.159G>A p.Pro53= synonymous_variant 2/7 ENST00000274368.9
CRHBPXM_047416736.1 linkuse as main transcriptc.-74G>A 5_prime_UTR_variant 1/6
CRHBPXR_948235.4 linkuse as main transcriptn.249G>A non_coding_transcript_exon_variant 2/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRHBPENST00000274368.9 linkuse as main transcriptc.159G>A p.Pro53= synonymous_variant 2/71 NM_001882.4 P1
CRHBPENST00000506501.1 linkuse as main transcriptc.159G>A p.Pro53= synonymous_variant 2/51
CRHBPENST00000512446.1 linkuse as main transcriptn.262G>A non_coding_transcript_exon_variant 1/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00513
AC:
781
AN:
152172
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00138
Gnomad AMI
AF:
0.118
Gnomad AMR
AF:
0.000982
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00339
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00808
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00412
AC:
966
AN:
234540
Hom.:
5
AF XY:
0.00387
AC XY:
496
AN XY:
128116
show subpopulations
Gnomad AFR exome
AF:
0.000993
Gnomad AMR exome
AF:
0.000952
Gnomad ASJ exome
AF:
0.00475
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000446
Gnomad FIN exome
AF:
0.00267
Gnomad NFE exome
AF:
0.00744
Gnomad OTH exome
AF:
0.00504
GnomAD4 exome
AF:
0.00635
AC:
9256
AN:
1456824
Hom.:
53
Cov.:
31
AF XY:
0.00617
AC XY:
4472
AN XY:
724210
show subpopulations
Gnomad4 AFR exome
AF:
0.000958
Gnomad4 AMR exome
AF:
0.00122
Gnomad4 ASJ exome
AF:
0.00500
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000575
Gnomad4 FIN exome
AF:
0.00305
Gnomad4 NFE exome
AF:
0.00767
Gnomad4 OTH exome
AF:
0.00516
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00513
AC:
781
AN:
152288
Hom.:
8
Cov.:
33
AF XY:
0.00465
AC XY:
346
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00137
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00339
Gnomad4 NFE
AF:
0.00808
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00464
Hom.:
2
Bravo
AF:
0.00519
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
7.1
Dann
Benign
0.96

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

LitVar

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

Other links and lift over

dbSNP: rs78115247; hg19: chr5-76249503; API