Variant rs41272246 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001882.4(CRHBP):c.81+22C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,607,350 control chromosomes in the GnomAD database, including 1,234 homozygotes. 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: 𝑓 0.037 ( 100 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1134 hom. )

Consequence

CRHBP
NM_001882.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Variant links:

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]

CRHBP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0365 (5562/152316) while in subpopulation NFE AF= 0.0411 (2795/68018). AF 95% confidence interval is 0.0398. There are 100 homozygotes in gnomad4. There are 2636 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHBP	NM_001882.4 link	c.81+22C>A		intron_variant		ENST00000274368.9	NP_001873.2	P24387
CRHBP	XR_948235.4 link	n.171+22C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9 link	c.81+22C>A		intron_variant		1	NM_001882.4	ENSP00000274368.4		P24387
CRHBP	ENST00000506501.1 link	c.81+22C>A		intron_variant		1		ENSP00000426097.1		D6RHH7

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5558

AN:

152198

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.0659

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0248

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0344

AC:

8522

AN:

247972

Hom.:

135

AF XY:

0.0346

AC XY:

4641

AN XY:

134200

show subpopulations

Gnomad AFR exome

AF:

0.0333

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0677

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.0428

Gnomad NFE exome

AF:

0.0424

Gnomad OTH exome

AF:

0.0388

GnomAD4 exome

AF:

0.0388

AC:

56490

AN:

1455034

Hom.:

1134

Cov.:

AF XY:

0.0385

AC XY:

27867

AN XY:

724310

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.0638

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0248

Gnomad4 FIN exome

AF:

0.0448

Gnomad4 NFE exome

AF:

0.0413

Gnomad4 OTH exome

AF:

0.0379

GnomAD4 genome

AF:

0.0365

AC:

5562

AN:

152316

Hom.:

100

Cov.:

AF XY:

0.0354

AC XY:

2636

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.0620

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0248

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0411

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0403

Hom.:

Bravo

AF:

0.0358

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.7

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over