NM_001882.4:c.693+1042G>A

Variant names:

• chr5-76959931-G-A
• rs6453267
• NM_001882.4:c.693+1042G>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.693+1042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 152,186 control chromosomes in the GnomAD database, including 1,150 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 0.070 (1150 hom., cov: 32)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.693+1042G>A		intron_variant	Intron 5 of 6	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.507+1042G>A		intron_variant	Intron 4 of 5		XP_047272692.1
CRHBP	XR_948235.4	n.783+1042G>A		intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.693+1042G>A		intron_variant	Intron 5 of 6	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000514258.1	n.193+1042G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10616 AN: 152068 Hom.: 1149 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0699 AC: 10640 AN: 152186 Hom.: 1150 Cov.: 32 AF XY: 0.0693 AC XY: 5157 AN XY: 74412

African (AFR) AF: 0.235 AC: 9754 AN: 41474

American (AMR) AF: 0.0309 AC: 472 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0343 AC: 165 AN: 4814

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68034

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.00222 Hom.: 4

Bravo AF: 0.0797

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-0.016
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: rs6453267; hg19: chr5-76255756;