rs10473984

Variant names:

• chr5-76971301-G-T
• rs10473984
• ENST00000514258.1:n.312-5064G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000514258.1(CRHBP):​n.312-5064G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,202 control chromosomes in the GnomAD database, including 2,016 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 0.11 (2016 hom., cov: 32)
• Consequence: CRHBP ENST00000514258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.902-5064G>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.312-5064G>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17152 AN: 152084 Hom.: 2010 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.113 AC: 17190 AN: 152202 Hom.: 2016 Cov.: 32 AF XY: 0.108 AC XY: 8072 AN XY: 74422

African (AFR) AF: 0.299 AC: 12424 AN: 41484

American (AMR) AF: 0.0642 AC: 981 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4830

European-Finnish (FIN) AF: 0.0237 AC: 251 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0403 AC: 2744 AN: 68018

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.0736 Hom.: 1948

Bravo AF: 0.127

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs10473984; hg19: chr5-76267126;