5-76955147-T-C

Variant names:

• chr5-76955147-T-C
• rs32897
• NM_001882.4:c.334-506T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001882.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	NM_001882.4	MANE Select	c.334-506T>C		intron	N/A	NP_001873.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	ENST00000274368.9	TSL:1 MANE Select	c.334-506T>C		intron	N/A	ENSP00000274368.4
	CRHBP	ENST00000506501.1	TSL:1	c.334-506T>C		intron	N/A	ENSP00000426097.1
	CRHBP	ENST00000512446.1	TSL:2	n.437-506T>C		intron	N/A

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

African (AFR) AF: 0.301 AC: 12470 AN: 41458

American (AMR) AF: 0.159 AC: 2427 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1142 AN: 5182

South Asian (SAS) AF: 0.163 AC: 787 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2431 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11365 AN: 68006

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.175 Hom.: 4155

Bravo AF: 0.208

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.88
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs32897; hg19: chr5-76250972;