chr5-76968796-G-A

Variant names:

• chr5-76968796-G-A
• rs757944609
• NM_001882.4:c.880G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001882.4(CRHBP):​c.880G>A​(p.Val294Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CRHBP NM_001882.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.880G>A	p.Val294Met	missense_variant	Exon 7 of 7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.694G>A	p.Val232Met	missense_variant	Exon 6 of 6		XP_047272692.1
CRHBP	XR_948235.4	n.901+5336G>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.880G>A	p.Val294Met	missense_variant	Exon 7 of 7	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000503763.1	n.295G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
CRHBP	ENST00000514258.1	n.311+5336G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251356 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135862

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 SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727226

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: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.26	B
Vest4		0.44
MutPred		0.87		Loss of sheet (P = 0.0357);
MVP		0.40
MPC		0.81
ClinPred		0.69	D
GERP RS		3.6
Varity_R		0.29
gMVP		0.74

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

Other links and lift over

dbSNP: rs757944609; hg19: chr5-76264621; COSMIC: COSV99169524;