rs10514082

chr5-76970622-A-G

Variant summary

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

The ENST00000514258.1(CRHBP):n.312-5743A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,206 control chromosomes in the GnomAD database, including 1,557 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 0.13 (1557 hom., cov: 32)
• Consequence: CRHBP ENST00000514258.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHBP	XR_948235.4	n.902-5743A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHBP	ENST00000514258.1	n.312-5743A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20472 AN: 152088 Hom.: 1557 Cov.: 32

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.135 AC: 20486 AN: 152206 Hom.: 1557 Cov.: 32 AF XY: 0.139 AC XY: 10347 AN XY: 74384

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.125

Alfa AF: 0.144 Hom.: 3387

Bravo AF: 0.123

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.060
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514082; hg19: chr5-76266447;