5-76981013-G-C

Position:

• chr5-76981013-G-C

Variant summary

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

The ENST00000514258.1(CRHBP):​n.520G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,990 control chromosomes in the GnomAD database, including 17,932 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 0.46 (17930 hom., cov: 32)
  • Exomes 𝑓: 0.37 (2 hom.)
• Consequence: CRHBP ENST00000514258.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.1110G>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.520G>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69658 AN: 151842 Hom.: 17897 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.367 AC: 11 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.459 AC: 69740 AN: 151960 Hom.: 17930 Cov.: 32 AF XY: 0.460 AC XY: 34153 AN XY: 74282

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.459

Alfa AF: 0.230 Hom.: 485

Bravo AF: 0.464

Asia WGS AF: 0.510 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1500; hg19: chr5-76276838;