Genetic Variant NM_001882.4:c.811+65T>C (chr5-76963525-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.811+65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,357,524 control chromosomes in the GnomAD database, including 126,029 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 0.51 ( 21826 hom., cov: 31)

Exomes 𝑓: 0.41 ( 104203 hom. )

Consequence

CRHBP
NM_001882.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.925

Publications

27 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHBP	NM_001882.4	MANE Select	c.811+65T>C		intron	N/A	NP_001873.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CRHBP	ENST00000274368.9	TSL:1 MANE Select	c.811+65T>C	intron	N/A	ENSP00000274368.4
CRHBP	ENST00000503763.1	TSL:2	n.226+65T>C	intron	N/A
CRHBP	ENST00000514258.1	TSL:3	n.311+65T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77208

AN:

151772

Hom.:

21772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.761

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.501

GnomAD4 exome

AF:

0.407

AC:

490202

AN:

1205634

Hom.:

104203

AF XY:

0.409

AC XY:

248945

AN XY:

608416

show subpopulations

African (AFR)

AF:

0.772

AC:

21166

AN:

27420

American (AMR)

AF:

0.360

AC:

13538

AN:

37656

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

11183

AN:

23314

East Asian (EAS)

AF:

0.573

AC:

21799

AN:

38020

South Asian (SAS)

AF:

0.473

AC:

35949

AN:

75946

European-Finnish (FIN)

AF:

0.464

AC:

24368

AN:

52494

Middle Eastern (MID)

AF:

0.497

AC:

2453

AN:

4932

European-Non Finnish (NFE)

AF:

0.377

AC:

337307

AN:

894146

Other (OTH)

AF:

0.434

AC:

22439

AN:

51706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13651

27302

40952

54603

68254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9934

19868

29802

39736

49670

<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:

0.509

AC:

77311

AN:

151890

Hom.:

21826

Cov.:

AF XY:

0.508

AC XY:

37728

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.761

AC:

31518

AN:

41406

American (AMR)

AF:

0.415

AC:

6327

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1641

AN:

3468

East Asian (EAS)

AF:

0.559

AC:

2877

AN:

5148

South Asian (SAS)

AF:

0.465

AC:

2235

AN:

4804

European-Finnish (FIN)

AF:

0.463

AC:

4877

AN:

10528

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.386

AC:

26229

AN:

67968

Other (OTH)

AF:

0.505

AC:

1060

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1699

3398

5097

6796

8495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.418

Hom.:

9909

Bravo

AF:

0.516

Asia WGS

AF:

0.518

AC:

1803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.31

(source)

DANN

Benign

0.30

PhyloP100

-0.93

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