5-76954762-G-A

Position:

• chr5-76954762-G-A

Variant summary

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

The ENST00000274368.9(CRHBP):​c.333+576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,966 control chromosomes in the GnomAD database, including 5,605 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 0.27 (5605 hom., cov: 32)
• Consequence: CRHBP ENST00000274368.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.333+576G>A		intron_variant		ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.147+576G>A		intron_variant			XP_047272692.1
CRHBP	XR_948235.4	n.423+576G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.333+576G>A		intron_variant		1	NM_001882.4	ENSP00000274368	P1
CRHBP	ENST00000506501.1	c.333+576G>A		intron_variant		1		ENSP00000426097
CRHBP	ENST00000512446.1	n.436+576G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40478 AN: 151848 Hom.: 5599 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.267 AC: 40508 AN: 151966 Hom.: 5605 Cov.: 32 AF XY: 0.263 AC XY: 19548 AN XY: 74274

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.298

Alfa AF: 0.257 Hom.: 821

Bravo AF: 0.276

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.92

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: rs3811939; hg19: chr5-76250587;