rs41272246

chr5-76953237-C-Achr5-76953237-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001882.4(CRHBP):c.81+22C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,607,350 control chromosomes in the GnomAD database, including 1,234 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 0.037 (100 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1134 hom.)
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0365 (5562/152316) while in subpopulation NFE AF= 0.0411 (2795/68018). AF 95% confidence interval is 0.0398. There are 100 homozygotes in gnomad4. There are 2636 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 100 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHBP	NM_001882.4	c.81+22C>A		intron_variant		ENST00000274368.9
CRHBP	XR_948235.4	n.171+22C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHBP	ENST00000274368.9	c.81+22C>A		intron_variant		1	NM_001882.4	P1
CRHBP	ENST00000506501.1	c.81+22C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5558 AN: 152198 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0425

GnomAD3 exomes AF: 0.0344 AC: 8522 AN: 247972 Hom.: 135 AF XY: 0.0346 AC XY: 4641 AN XY: 134200

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.0677

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0242

Gnomad FIN exome AF: 0.0428

Gnomad NFE exome AF: 0.0424

Gnomad OTH exome AF: 0.0388

GnomAD4 exome AF: 0.0388 AC: 56490 AN: 1455034 Hom.: 1134 Cov.: 29 AF XY: 0.0385 AC XY: 27867 AN XY: 724310

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0638

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.0448

Gnomad4 NFE exome AF: 0.0413

Gnomad4 OTH exome AF: 0.0379

GnomAD4 genome AF: 0.0365 AC: 5562 AN: 152316 Hom.: 100 Cov.: 33 AF XY: 0.0354 AC XY: 2636 AN XY: 74480

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0403 Hom.: 27

Bravo AF: 0.0358

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.7
Dann	Benign	0.77

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: rs41272246; hg19: chr5-76249062;