5-76966939-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHBP	NM_001882.4	c.812-1789C>T		intron_variant		ENST00000274368.9
CRHBP	XM_047416736.1	c.626-1789C>T		intron_variant
CRHBP	XR_948235.4	n.901+3479C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHBP	ENST00000274368.9	c.812-1789C>T		intron_variant		1	NM_001882.4	P1
CRHBP	ENST00000503763.1	n.227-1789C>T		intron_variant, non_coding_transcript_variant		2
CRHBP	ENST00000514258.1	n.311+3479C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.491

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.5
Dann	Benign	0.70

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: rs7721519; hg19: chr5-76262764;