5-76953678-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.159G>A	p.Pro53Pro	synonymous_variant	Exon 2 of 7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.-74G>A		5_prime_UTR_variant	Exon 1 of 6		XP_047272692.1
CRHBP	XR_948235.4	n.249G>A		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.159G>A	p.Pro53Pro	synonymous_variant	Exon 2 of 7	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000506501.1	c.159G>A	p.Pro53Pro	synonymous_variant	Exon 2 of 5	1		ENSP00000426097.1
CRHBP	ENST00000512446.1	n.262G>A		non_coding_transcript_exon_variant	Exon 1 of 4	2

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

GnomAD3 exomes AF: 0.00412 AC: 966 AN: 234540 Hom.: 5 AF XY: 0.00387 AC XY: 496 AN XY: 128116

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 SAS exome AF: 0.000446

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

Gnomad4 AFR exome AF: 0.000958

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000575

Gnomad4 FIN exome AF: 0.00305

Gnomad4 NFE exome AF: 0.00767

Gnomad4 OTH exome AF: 0.00516

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

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00808

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00464 Hom.: 2

Bravo AF: 0.00519

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.1
DANN	Benign	0.96

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: rs78115247; hg19: chr5-76249503;