rs7721519

Positions:

• chr5-76966939-C-G
• chr5-76966939-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000274368.9(CRHBP):​c.812-1789C>G 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: 33)
• Consequence: CRHBP ENST00000274368.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.812-1789C>G		intron_variant		ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.626-1789C>G		intron_variant			XP_047272692.1
CRHBP	XR_948235.4	n.901+3479C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.812-1789C>G		intron_variant		1	NM_001882.4	ENSP00000274368	P1
CRHBP	ENST00000503763.1	n.227-1789C>G		intron_variant, non_coding_transcript_variant		2
CRHBP	ENST00000514258.1	n.311+3479C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.63

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: rs7721519; hg19: chr5-76262764;