rs10474485

Variant names:

• chr5-76975028-C-A
• rs10474485
• ENST00000514258.1:n.312-1337C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76975028-C-A
• chr5-76975028-C-T

Variant summary

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

The ENST00000514258.1(CRHBP):​n.312-1337C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,070 control chromosomes in the GnomAD database, including 5,672 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 0.26 (5672 hom., cov: 32)
• Consequence: CRHBP ENST00000514258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 20 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.902-1337C>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.312-1337C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39250 AN: 151952 Hom.: 5659 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.258 AC: 39293 AN: 152070 Hom.: 5672 Cov.: 32 AF XY: 0.258 AC XY: 19208 AN XY: 74340

African (AFR) AF: 0.385 AC: 15931 AN: 41420

American (AMR) AF: 0.212 AC: 3237 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1992 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4828

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10586

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13117 AN: 67996

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.216 Hom.: 16395

Bravo AF: 0.264

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.55
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10474485; hg19: chr5-76270853;