7-30655713-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001883.5(CRHR2):c.920A>G(p.Lys307Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CRHR2
NM_001883.5 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.99

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]

CRHR2 links:

LOC124901609 (HGNC:):

LOC124901609 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016458094).

BP6

Variant 7-30655713-T-C is Benign according to our data. Variant chr7-30655713-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 726063.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-30655713-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5 linkuse as main transcript	c.920A>G	p.Lys307Arg	missense_variant, splice_region_variant	10/12	ENST00000471646.6
LOC124901609	XR_007060276.1 linkuse as main transcript	n.1917T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6 linkuse as main transcript	c.920A>G	p.Lys307Arg	missense_variant, splice_region_variant	10/12	1	NM_001883.5	P1	Q13324-1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000380

AC:

AN:

249956

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.00554

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

202

AN:

1460910

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152358

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.00167

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000519

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.5

D;N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.032

D;D;D;D

Polyphen

1.0, 0.98, 1.0

.;D;D;D

Vest4

0.82

MVP

0.71

MPC

0.28

ClinPred

0.11

GERP RS

5.1

Varity_R

0.72

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over