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5-76954120-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001882.4(CRHBP):c.267C>G(p.Pro89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,046 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

CRHBP
NM_001882.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.92
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 -15 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=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-76954120-C-G is Benign according to our data. Variant chr5-76954120-C-G is described in ClinVar as [Benign]. Clinvar id is 773933.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=-4.92 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1533/152310) while in subpopulation AFR AF= 0.0345 (1434/41568). AF 95% confidence interval is 0.033. There are 25 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
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 25 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRHBPNM_001882.4 linkuse as main transcriptc.267C>G p.Pro89= synonymous_variant 3/7 ENST00000274368.9
CRHBPXM_047416736.1 linkuse as main transcriptc.81C>G p.Pro27= synonymous_variant 2/6
CRHBPXR_948235.4 linkuse as main transcriptn.357C>G non_coding_transcript_exon_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRHBPENST00000274368.9 linkuse as main transcriptc.267C>G p.Pro89= synonymous_variant 3/71 NM_001882.4 P1
CRHBPENST00000506501.1 linkuse as main transcriptc.267C>G p.Pro89= synonymous_variant 3/51
CRHBPENST00000512446.1 linkuse as main transcriptn.370C>G non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0100
AC:
1527
AN:
152192
Hom.:
25
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0345
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00497
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00243
AC:
610
AN:
250840
Hom.:
12
AF XY:
0.00172
AC XY:
233
AN XY:
135636
show subpopulations
Gnomad AFR exome
AF:
0.0330
Gnomad AMR exome
AF:
0.00150
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000971
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00107
AC:
1571
AN:
1461736
Hom.:
24
Cov.:
31
AF XY:
0.000869
AC XY:
632
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.0364
Gnomad4 AMR exome
AF:
0.00221
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000782
Gnomad4 OTH exome
AF:
0.00250
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1533
AN:
152310
Hom.:
25
Cov.:
33
AF XY:
0.0100
AC XY:
748
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0345
Gnomad4 AMR
AF:
0.00496
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00276
Hom.:
0
Bravo
AF:
0.0117
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

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 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
0.34
Dann
Benign
0.85

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: rs34761141; hg19: chr5-76249945; API