chr5-76978712-T-C

Variant names:

• chr5-76978712-T-C
• rs1715747
• ENST00000514258.1:n.467+2192T>C

Variant summary

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

The ENST00000514258.1(CRHBP):​n.467+2192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,050 control chromosomes in the GnomAD database, including 17,740 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 (17740 hom., cov: 32)
• Consequence: CRHBP ENST00000514258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.1057+2192T>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.467+2192T>C		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69491 AN: 151932 Hom.: 17706 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.458 AC: 69572 AN: 152050 Hom.: 17740 Cov.: 32 AF XY: 0.459 AC XY: 34092 AN XY: 74328

African (AFR) AF: 0.690 AC: 28596 AN: 41464

American (AMR) AF: 0.368 AC: 5631 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.583 AC: 3014 AN: 5174

South Asian (SAS) AF: 0.423 AC: 2038 AN: 4820

European-Finnish (FIN) AF: 0.426 AC: 4501 AN: 10566

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23054 AN: 67962

Other (OTH) AF: 0.460 AC: 971 AN: 2112

Alfa AF: 0.381 Hom.: 36890

Bravo AF: 0.462

Asia WGS AF: 0.513 AC: 1786 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	3.8
DANN	Benign	0.62
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs1715747; hg19: chr5-76274537;