rs7728378

Variant names:

• chr5-76963525-T-A
• rs7728378
• NM_001882.4:c.811+65T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76963525-T-A
• chr5-76963525-T-C
• chr5-76963525-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001882.4(CRHBP):​c.811+65T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRHBP NM_001882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 27 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.811+65T>A		intron_variant	Intron 6 of 6	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.625+65T>A		intron_variant	Intron 5 of 5		XP_047272692.1
CRHBP	XR_948235.4	n.901+65T>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.811+65T>A		intron_variant	Intron 6 of 6	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000503763.1	n.226+65T>A		intron_variant	Intron 1 of 1	2
CRHBP	ENST00000514258.1	n.311+65T>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1208590 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 609834

African (AFR) AF: 0.00 AC: 0 AN: 27472

American (AMR) AF: 0.00 AC: 0 AN: 37724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23352

East Asian (EAS) AF: 0.00 AC: 0 AN: 38068

South Asian (SAS) AF: 0.00 AC: 0 AN: 76152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 896518

Other (OTH) AF: 0.00 AC: 0 AN: 51812

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9909

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.44
PhyloP100		-0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7728378; hg19: chr5-76259350;