chr5-76963525-T-C

Position:

• chr5-76963525-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000274368.9(CRHBP):​c.811+65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,357,524 control chromosomes in the GnomAD database, including 126,029 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 0.51 (21826 hom., cov: 31)
  • Exomes 𝑓: 0.41 (104203 hom.)
• Consequence: CRHBP ENST00000274368.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.811+65T>C		intron_variant		ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.625+65T>C		intron_variant			XP_047272692.1
CRHBP	XR_948235.4	n.901+65T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.811+65T>C		intron_variant		1	NM_001882.4	ENSP00000274368	P1
CRHBP	ENST00000503763.1	n.226+65T>C		intron_variant, non_coding_transcript_variant		2
CRHBP	ENST00000514258.1	n.311+65T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77208 AN: 151772 Hom.: 21772 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.407 AC: 490202 AN: 1205634 Hom.: 104203 AF XY: 0.409 AC XY: 248945 AN XY: 608416

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.509 AC: 77311 AN: 151890 Hom.: 21826 Cov.: 31 AF XY: 0.508 AC XY: 37728 AN XY: 74210

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.505

Alfa AF: 0.413 Hom.: 7094

Bravo AF: 0.516

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7728378; hg19: chr5-76259350; COSMIC: COSV57190256; COSMIC: COSV57190256;