rs32897

Positions:

• chr5-76955147-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001882.4(CRHBP):​c.334-506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,124 control chromosomes in the GnomAD database, including 3,632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3632 hom., cov: 32)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHBP	NM_001882.4	c.334-506T>C		intron_variant		ENST00000274368.9
CRHBP	XM_047416736.1	c.148-506T>C		intron_variant
CRHBP	XR_948235.4	n.424-506T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHBP	ENST00000274368.9	c.334-506T>C		intron_variant		1	NM_001882.4	P1
CRHBP	ENST00000506501.1	c.334-506T>C		intron_variant		1
CRHBP	ENST00000512446.1	n.437-506T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31654 AN: 152006 Hom.: 3626 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31692 AN: 152124 Hom.: 3632 Cov.: 32 AF XY: 0.207 AC XY: 15418 AN XY: 74368

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.198

Alfa AF: 0.171 Hom.: 3129

Bravo AF: 0.208

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.88

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: rs32897; hg19: chr5-76250972;