rs10055255

Variant names:

• chr5-76968168-A-T
• rs10055255
• NM_001882.4:c.812-560A>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.812-560A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,152 control chromosomes in the GnomAD database, including 20,364 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 (20364 hom., cov: 30)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 27 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.812-560A>T		intron_variant	Intron 6 of 6	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.626-560A>T		intron_variant	Intron 5 of 5		XP_047272692.1
CRHBP	XR_948235.4	n.901+4708A>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.812-560A>T		intron_variant	Intron 6 of 6	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000503763.1	n.227-560A>T		intron_variant	Intron 1 of 1	2
CRHBP	ENST00000514258.1	n.311+4708A>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 74761 AN: 151044 Hom.: 20315 Cov.: 30

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.513

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: 0.495 AC: 74854 AN: 151152 Hom.: 20364 Cov.: 30 AF XY: 0.495 AC XY: 36520 AN XY: 73750

African (AFR) AF: 0.727 AC: 29931 AN: 41194

American (AMR) AF: 0.399 AC: 6072 AN: 15208

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

East Asian (EAS) AF: 0.568 AC: 2931 AN: 5158

South Asian (SAS) AF: 0.464 AC: 2226 AN: 4794

European-Finnish (FIN) AF: 0.460 AC: 4665 AN: 10152

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25825 AN: 67874

Other (OTH) AF: 0.491 AC: 1033 AN: 2102

Alfa AF: 0.441 Hom.: 1979

Bravo AF: 0.501

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.87
DANN	Benign	0.62
PhyloP100		-1.1
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: rs10055255; hg19: chr5-76263993;