rs3811939

Variant names:

• chr5-76954762-G-A
• rs3811939
• NM_001882.4:c.333+576G>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.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 NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 12 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=-0.82).
• 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 rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.333+576G>A		intron_variant	Intron 3 of 6	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.147+576G>A		intron_variant	Intron 2 of 5		XP_047272692.1
CRHBP	XR_948235.4	n.423+576G>A		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.333+576G>A		intron_variant	Intron 3 of 6	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000506501.1	c.333+576G>A		intron_variant	Intron 3 of 4	1		ENSP00000426097.1
CRHBP	ENST00000512446.1	n.436+576G>A		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.303 AC: 12569 AN: 41424

American (AMR) AF: 0.248 AC: 3794 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1304 AN: 5152

South Asian (SAS) AF: 0.128 AC: 618 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2457 AN: 10548

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17458 AN: 67966

Other (OTH) AF: 0.298 AC: 628 AN: 2110

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
PhyloP100		-0.90
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: rs3811939; hg19: chr5-76250587;