rs2014663

Variant summary

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

The NM_001883.5(CRHR2):​c.229+5958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,232 control chromosomes in the GnomAD database, including 58,242 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 0.87 ( 58242 hom., cov: 32)

Consequence

CRHR2
NM_001883.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

Publications

8 publications found
Variant links:
Genes affected
CRHR2 (HGNC:2358): (corticotropin releasing hormone receptor 2) The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]

Genome browser will be placed here

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=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRHR2NM_001883.5 linkc.229+5958G>A intron_variant Intron 2 of 11 ENST00000471646.6 NP_001874.2 Q13324-1A0A090N7T4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRHR2ENST00000471646.6 linkc.229+5958G>A intron_variant Intron 2 of 11 1 NM_001883.5 ENSP00000418722.1 Q13324-1

Frequencies

GnomAD3 genomes
AF:
0.871
AC:
132483
AN:
152114
Hom.:
58184
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.969
Gnomad AMI
AF:
0.863
Gnomad AMR
AF:
0.855
Gnomad ASJ
AF:
0.884
Gnomad EAS
AF:
0.615
Gnomad SAS
AF:
0.731
Gnomad FIN
AF:
0.802
Gnomad MID
AF:
0.876
Gnomad NFE
AF:
0.854
Gnomad OTH
AF:
0.878
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.871
AC:
132600
AN:
152232
Hom.:
58242
Cov.:
32
AF XY:
0.864
AC XY:
64282
AN XY:
74422
show subpopulations
African (AFR)
AF:
0.969
AC:
40275
AN:
41566
American (AMR)
AF:
0.856
AC:
13094
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.884
AC:
3068
AN:
3470
East Asian (EAS)
AF:
0.615
AC:
3176
AN:
5166
South Asian (SAS)
AF:
0.732
AC:
3521
AN:
4812
European-Finnish (FIN)
AF:
0.802
AC:
8495
AN:
10588
Middle Eastern (MID)
AF:
0.880
AC:
257
AN:
292
European-Non Finnish (NFE)
AF:
0.854
AC:
58081
AN:
68014
Other (OTH)
AF:
0.875
AC:
1849
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
866
1732
2599
3465
4331
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
888
1776
2664
3552
4440
<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:
0.861
Hom.:
167140
Bravo
AF:
0.881
Asia WGS
AF:
0.723
AC:
2516
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.24
DANN
Benign
0.32
PhyloP100
-0.78
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2014663; hg19: chr7-30715573; API