7-30653516-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001883.5(CRHR2):​c.1180C>T​(p.Pro394Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CRHR2
NM_001883.5 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.11
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39263391).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRHR2NM_001883.5 linkuse as main transcriptc.1180C>T p.Pro394Ser missense_variant 12/12 ENST00000471646.6 NP_001874.2
LOC124901609XR_007060276.1 linkuse as main transcriptn.522-802G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRHR2ENST00000471646.6 linkuse as main transcriptc.1180C>T p.Pro394Ser missense_variant 12/121 NM_001883.5 ENSP00000418722 P1Q13324-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 14, 2022The c.1261C>T (p.P421S) alteration is located in exon 13 (coding exon 13) of the CRHR2 gene. This alteration results from a C to T substitution at nucleotide position 1261, causing the proline (P) at amino acid position 421 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.066
.;T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.39
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.1
.;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.21
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.011
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.44
MutPred
0.23
.;Gain of MoRF binding (P = 0.0369);.;
MVP
0.80
MPC
0.91
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.23
gMVP
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-30693132; API