rs10062367

Variant names:

• chr5-76968529-G-A
• rs10062367
• NM_001882.4:c.812-199G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 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.812-199G>A		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.812-199G>A		intron	N/A	ENSP00000274368.4
	CRHBP	ENST00000503763.1	TSL:2	n.227-199G>A		intron	N/A
	CRHBP	ENST00000514258.1	TSL:3	n.311+5069G>A		intron	N/A

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

African (AFR) AF: 0.372 AC: 15429 AN: 41424

American (AMR) AF: 0.191 AC: 2923 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3460

East Asian (EAS) AF: 0.189 AC: 978 AN: 5178

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4820

European-Finnish (FIN) AF: 0.247 AC: 2600 AN: 10514

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12759 AN: 67982

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.202 Hom.: 5488

Bravo AF: 0.248

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.23
PhyloP100		0.20
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: rs10062367; hg19: chr5-76264354;