rs1053989

Positions:

• chr5-76969210-C-A
• chr5-76969210-C-T

Variant summary

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

The NM_001882.4(CRHBP):​c.*325C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 203,854 control chromosomes in the GnomAD database, including 25,328 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 (20587 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4741 hom.)
• Consequence: CRHBP NM_001882.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.*325C>A		3_prime_UTR_variant	7/7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.*325C>A		3_prime_UTR_variant	6/6		XP_047272692.1
CRHBP	XR_948235.4	n.901+5750C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.*325C>A		3_prime_UTR_variant	7/7	1	NM_001882.4	ENSP00000274368	P1
CRHBP	ENST00000514258.1	n.311+5750C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75366 AN: 151942 Hom.: 20536 Cov.: 33

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.418 AC: 21631 AN: 51794 Hom.: 4741 Cov.: 0 AF XY: 0.414 AC XY: 10760 AN XY: 25996

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.582

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.496 AC: 75465 AN: 152060 Hom.: 20587 Cov.: 33 AF XY: 0.497 AC XY: 36894 AN XY: 74300

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.491

Alfa AF: 0.399 Hom.: 20899

Bravo AF: 0.502

Asia WGS AF: 0.505 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.49

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: rs1053989; hg19: chr5-76265035;