Variant 5-76953668-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001882.4(CRHBP):c.149G>C(p.Gly50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 6.9e-7 ( 0 hom. )

Consequence

CRHBP
NM_001882.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07916018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CRHBP	NM_001882.4 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	2/7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1 linkuse as main transcript	c.-84G>C		5_prime_UTR_variant	1/6		XP_047272692.1
CRHBP	XR_948235.4 linkuse as main transcript	n.239G>C		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CRHBP	ENST00000274368.9 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	2/7	1	NM_001882.4	ENSP00000274368	P1
CRHBP	ENST00000506501.1 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	2/5	1		ENSP00000426097
CRHBP	ENST00000512446.1 linkuse as main transcript	n.252G>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724516

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.149G>C (p.G50A) alteration is located in exon 2 (coding exon 2) of the CRHBP gene. This alteration results from a G to C substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 to be replaced by an alanine (A). 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

0.086

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.018

Sift

Benign

0.71

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.39

Loss of loop (P = 0.0235);Loss of loop (P = 0.0235);

MVP

0.082

MPC

0.59

ClinPred

0.13

GERP RS

0.68

Varity_R

0.035

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over