rs34761141

Variant names:

• chr5-76954120-C-G
• rs34761141
• NM_001882.4:c.267C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-76954120-C-G
• chr5-76954120-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001882.4(CRHBP):​c.267C>G​(p.Pro89Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,046 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (25 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: CRHBP NM_001882.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.92
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-76954120-C-G is Benign according to our data. Variant chr5-76954120-C-G is described in ClinVar as Benign. ClinVar VariationId is 773933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.92 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1533/152310) while in subpopulation AFR AF = 0.0345 (1434/41568). AF 95% confidence interval is 0.033. There are 25 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 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.267C>G	p.Pro89Pro	synonymous	Exon 3 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.267C>G	p.Pro89Pro	synonymous	Exon 3 of 7	ENSP00000274368.4	P24387
	CRHBP	ENST00000506501.1	TSL:1	c.267C>G	p.Pro89Pro	synonymous	Exon 3 of 5	ENSP00000426097.1	D6RHH7
	CRHBP	ENST00000909957.1		c.267C>G	p.Pro89Pro	synonymous	Exon 3 of 8	ENSP00000580016.1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1527 AN: 152192 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00243 AC: 610 AN: 250840 AF XY: 0.00172

Gnomad AFR exome AF: 0.0330

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00107 AC: 1571 AN: 1461736 Hom.: 24 Cov.: 31 AF XY: 0.000869 AC XY: 632 AN XY: 727192

African (AFR) AF: 0.0364 AC: 1219 AN: 33470

American (AMR) AF: 0.00221 AC: 99 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111930

Other (OTH) AF: 0.00250 AC: 151 AN: 60388

GnomAD4 genome AF: 0.0101 AC: 1533 AN: 152310 Hom.: 25 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74478

African (AFR) AF: 0.0345 AC: 1434 AN: 41568

American (AMR) AF: 0.00496 AC: 76 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00276 Hom.: 0

Bravo AF: 0.0117

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

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	-0.67
CADD	Benign	0.34
DANN	Benign	0.85
PhyloP100		-4.9
Mutation Taster		=99/1	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: rs34761141; hg19: chr5-76249945;