5-76953162-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001882.4(CRHBP):c.28C>A(p.His10Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CRHBP
NM_001882.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Publications

0 publications found

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]

CRHBP links:

S100Z (HGNC:30367): (S100 calcium binding protein Z) Members of the S100 protein family contain 2 calcium-binding EF-hands and exhibit cell-type specific expression patterns. For additional background information on S100 proteins, see MIM 114085.[supplied by OMIM, Mar 2008]

S100Z links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4 link	c.28C>A	p.His10Asn	missense_variant	Exon 1 of 7	ENST00000274368.9	NP_001873.2	P24387
CRHBP	XR_948235.4 link	n.118C>A		non_coding_transcript_exon_variant	Exon 1 of 8
S100Z	XM_011543241.3 link	c.*330C>A		downstream_gene_variant			XP_011541543.1	Q8WXG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9 link	c.28C>A	p.His10Asn	missense_variant	Exon 1 of 7	1	NM_001882.4	ENSP00000274368.4		P24387
CRHBP	ENST00000506501.1 link	c.28C>A	p.His10Asn	missense_variant	Exon 1 of 5	1		ENSP00000426097.1		D6RHH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250200

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.28C>A (p.H10N) alteration is located in exon 1 (coding exon 1) of the CRHBP gene. This alteration results from a C to A substitution at nucleotide position 28, causing the histidine (H) at amino acid position 10 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

3.9

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.11

Sift

Benign

0.40

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.81

P;P

Vest4

0.54

MutPred

0.64

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.27

MPC

1.1

ClinPred

0.94

GERP RS

4.8

PromoterAI

0.015

Neutral

(source)

Varity_R

0.17

gMVP

0.35

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-76953162-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over