5-76962223-A-G

Position:

• chr5-76962223-A-G

Variant summary

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

The NM_001882.4(CRHBP):​c.694-1120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,946 control chromosomes in the GnomAD database, including 21,020 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 (21020 hom., cov: 32)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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]

CRHBP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.694-1120A>G		intron_variant		ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.508-1120A>G		intron_variant			XP_047272692.1
CRHBP	XR_948235.4	n.784-1120A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.694-1120A>G		intron_variant		1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000514258.1	n.194-1120A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76117 AN: 151826 Hom.: 20969 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.502 AC: 76220 AN: 151946 Hom.: 21020 Cov.: 32 AF XY: 0.501 AC XY: 37217 AN XY: 74244

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.498

Alfa AF: 0.414 Hom.: 12684

Bravo AF: 0.508

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.9
DANN	Benign	0.64

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: rs7718461; hg19: chr5-76258048;