rs10062367

Positions:

• chr5-76968529-G-A

Variant summary

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

The NM_001882.4(CRHBP):​c.812-199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,964 control chromosomes in the GnomAD database, including 5,130 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 0.25 (5130 hom., cov: 32)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHBP	NM_001882.4	c.812-199G>A		intron_variant		ENST00000274368.9
CRHBP	XM_047416736.1	c.626-199G>A		intron_variant
CRHBP	XR_948235.4	n.901+5069G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHBP	ENST00000274368.9	c.812-199G>A		intron_variant		1	NM_001882.4	P1
CRHBP	ENST00000503763.1	n.227-199G>A		intron_variant, non_coding_transcript_variant		2
CRHBP	ENST00000514258.1	n.311+5069G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37372 AN: 151846 Hom.: 5118 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.246 AC: 37426 AN: 151964 Hom.: 5130 Cov.: 32 AF XY: 0.246 AC XY: 18287 AN XY: 74256

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.234

Alfa AF: 0.196 Hom.: 3999

Bravo AF: 0.248

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.23

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: rs10062367; hg19: chr5-76264354;