chr5-76970622-A-G

Variant names:

• chr5-76970622-A-G
• rs10514082
• ENST00000514258.1:n.312-5743A>G

Variant summary

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

The ENST00000514258.1(CRHBP):​n.312-5743A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 6 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=-0.98).
• 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 rank	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.902-5743A>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.312-5743A>G		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.0774 AC: 3215 AN: 41560

American (AMR) AF: 0.128 AC: 1957 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.189 AC: 977 AN: 5164

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2363 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10025 AN: 67998

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.142 Hom.: 7155

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
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10514082; hg19: chr5-76266447;