5-76969697-C-T

Variant names:

• chr5-76969697-C-T
• rs2174444
• ENST00000909956.1:c.*35+777C>T

Variant summary

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

The ENST00000909956.1(CRHBP):​c.*35+777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,028 control chromosomes in the GnomAD database, including 11,392 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 0.38 (11392 hom., cov: 32)
• Consequence: CRHBP ENST00000909956.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000909956.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	NM_001882.4	MANE Select	c.*812C>T		downstream_gene	N/A	NP_001873.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	ENST00000909956.1		c.*35+777C>T		intron	N/A	ENSP00000580015.1
	CRHBP	ENST00000514258.1	TSL:3	n.311+6237C>T		intron	N/A
	CRHBP	ENST00000274368.9	TSL:1 MANE Select	c.*812C>T		downstream_gene	N/A	ENSP00000274368.4	P24387

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58080 AN: 151910 Hom.: 11371 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.382 AC: 58139 AN: 152028 Hom.: 11392 Cov.: 32 AF XY: 0.387 AC XY: 28757 AN XY: 74292

African (AFR) AF: 0.426 AC: 17679 AN: 41464

American (AMR) AF: 0.335 AC: 5121 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2933 AN: 5162

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4812

European-Finnish (FIN) AF: 0.441 AC: 4642 AN: 10536

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23113 AN: 67996

Other (OTH) AF: 0.381 AC: 805 AN: 2114

Alfa AF: 0.280 Hom.: 1067

Bravo AF: 0.374

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs2174444; hg19: chr5-76265522;