rs78115247

Variant names:

• chr5-76953678-G-A
• rs78115247
• NM_001882.4:c.159G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76953678-G-A
• chr5-76953678-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001882.4(CRHBP):​c.159G>A​(p.Pro53Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,609,112 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (53 hom.)
• Consequence: CRHBP NM_001882.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0990
• Publications: 4 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-76953678-G-A is Benign according to our data. Variant chr5-76953678-G-A is described in ClinVar as Benign. ClinVar VariationId is 711390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.099 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001882.4. 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.159G>A	p.Pro53Pro	synonymous	Exon 2 of 7	NP_001873.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	ENST00000274368.9	TSL:1 MANE Select	c.159G>A	p.Pro53Pro	synonymous	Exon 2 of 7	ENSP00000274368.4	P24387
	CRHBP	ENST00000506501.1	TSL:1	c.159G>A	p.Pro53Pro	synonymous	Exon 2 of 5	ENSP00000426097.1	D6RHH7
	CRHBP	ENST00000909957.1		c.159G>A	p.Pro53Pro	synonymous	Exon 2 of 8	ENSP00000580016.1

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 781 AN: 152172 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00808

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00412 AC: 966 AN: 234540 AF XY: 0.00387

Gnomad AFR exome AF: 0.000993

Gnomad AMR exome AF: 0.000952

Gnomad ASJ exome AF: 0.00475

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00267

Gnomad NFE exome AF: 0.00744

Gnomad OTH exome AF: 0.00504

GnomAD4 exome AF: 0.00635 AC: 9256 AN: 1456824 Hom.: 53 Cov.: 31 AF XY: 0.00617 AC XY: 4472 AN XY: 724210

African (AFR) AF: 0.000958 AC: 32 AN: 33392

American (AMR) AF: 0.00122 AC: 54 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.00500 AC: 130 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.000575 AC: 49 AN: 85206

European-Finnish (FIN) AF: 0.00305 AC: 161 AN: 52714

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5728

European-Non Finnish (NFE) AF: 0.00767 AC: 8517 AN: 1109932

Other (OTH) AF: 0.00516 AC: 310 AN: 60080

GnomAD4 genome AF: 0.00513 AC: 781 AN: 152288 Hom.: 8 Cov.: 33 AF XY: 0.00465 AC XY: 346 AN XY: 74458

African (AFR) AF: 0.00137 AC: 57 AN: 41562

American (AMR) AF: 0.000981 AC: 15 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00808 AC: 550 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00464 Hom.: 2

Bravo AF: 0.00519

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.1
DANN	Benign	0.96
PhyloP100		-0.099
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs78115247; hg19: chr5-76249503;