5-76966939-C-T

Variant names:

• chr5-76966939-C-T
• rs7721519
• NM_001882.4:c.812-1789C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001882.4(CRHBP):​c.812-1789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,034 control chromosomes in the GnomAD database, including 20,517 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 0.50 (20517 hom., cov: 33)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 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.812-1789C>T		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.812-1789C>T		intron	N/A	ENSP00000274368.4
	CRHBP	ENST00000503763.1	TSL:2	n.227-1789C>T		intron	N/A
	CRHBP	ENST00000514258.1	TSL:3	n.311+3479C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75260 AN: 151916 Hom.: 20466 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.496 AC: 75359 AN: 152034 Hom.: 20517 Cov.: 33 AF XY: 0.496 AC XY: 36831 AN XY: 74304

African (AFR) AF: 0.727 AC: 30135 AN: 41470

American (AMR) AF: 0.400 AC: 6114 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3468

East Asian (EAS) AF: 0.566 AC: 2925 AN: 5172

South Asian (SAS) AF: 0.464 AC: 2238 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4889 AN: 10554

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25851 AN: 67952

Other (OTH) AF: 0.491 AC: 1037 AN: 2112

Alfa AF: 0.441 Hom.: 1977

Bravo AF: 0.501

Asia WGS AF: 0.507 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		0.015
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: rs7721519; hg19: chr5-76262764;