Genetic Variant CRHBP:c.*272T>C (chr5-76969157-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001882.4(CRHBP):c.*272T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 315,770 control chromosomes in the GnomAD database, including 23,451 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 0.38 ( 11458 hom., cov: 33)

Exomes 𝑓: 0.37 ( 11993 hom. )

Consequence

CRHBP
NM_001882.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

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.*272T>C		3_prime_UTR	Exon 7 of 7	NP_001873.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRHBP	ENST00000274368.9	TSL:1 MANE Select	c.*272T>C	3_prime_UTR	Exon 7 of 7	ENSP00000274368.4	P24387
CRHBP	ENST00000909957.1		c.*272T>C	3_prime_UTR	Exon 8 of 8	ENSP00000580016.1
CRHBP	ENST00000909956.1		c.*35+237T>C	intron	N/A	ENSP00000580015.1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58247

AN:

152018

Hom.:

11436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.376

GnomAD4 exome

AF:

0.371

AC:

60709

AN:

163634

Hom.:

11993

Cov.:

AF XY:

0.371

AC XY:

30924

AN XY:

83280

show subpopulations

African (AFR)

AF:

0.439

AC:

2230

AN:

5074

American (AMR)

AF:

0.319

AC:

1608

AN:

5036

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

2332

AN:

6162

East Asian (EAS)

AF:

0.596

AC:

7711

AN:

12940

South Asian (SAS)

AF:

0.403

AC:

2777

AN:

6894

European-Finnish (FIN)

AF:

0.430

AC:

4567

AN:

10622

Middle Eastern (MID)

AF:

0.435

AC:

362

AN:

832

European-Non Finnish (NFE)

AF:

0.333

AC:

35103

AN:

105270

Other (OTH)

AF:

0.372

AC:

4019

AN:

10804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1771

3542

5313

7084

8855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58307

AN:

152136

Hom.:

11458

Cov.:

AF XY:

0.388

AC XY:

28838

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.427

AC:

17731

AN:

41478

American (AMR)

AF:

0.336

AC:

5136

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1300

AN:

3470

East Asian (EAS)

AF:

0.573

AC:

2967

AN:

5178

South Asian (SAS)

AF:

0.438

AC:

2116

AN:

4830

European-Finnish (FIN)

AF:

0.440

AC:

4645

AN:

10566

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.341

AC:

23156

AN:

67996

Other (OTH)

AF:

0.380

AC:

805

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1861

3721

5582

7442

9303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.354

Hom.:

16286

Bravo

AF:

0.375

Asia WGS

AF:

0.483

AC:

1679

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

(source)

DANN

Benign

0.52

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over