Variant 7-30689292-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001202475.1(CRHR2):c.91-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,548,616 control chromosomes in the GnomAD database, including 260,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 18845 hom., cov: 33)

Exomes 𝑓: 0.58 ( 241204 hom. )

Consequence

CRHR2
NM_001202475.1 splice_region, intron

Scores

Splicing: ADA: 0.01359

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

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:

CRHR2 (HGNC:):

CRHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001202475.1 linkuse as main transcript	c.91-8T>A		splice_region_variant, intron_variant			NP_001189404.1	Q13324-2
CRHR2	NM_001202481.1 linkuse as main transcript	c.-260-8T>A		splice_region_variant, intron_variant			NP_001189410.1	Q13324-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
CRHR2	ENST00000348438.8 linkuse as main transcript	c.91-8T>A	splice_region_variant, intron_variant	1	ENSP00000340943.4	Q13324-2
CRHR2	ENST00000445981.5 linkuse as main transcript	c.91-8T>A	splice_region_variant, intron_variant	1	ENSP00000401241.1	C9JZM9
CRHR2	ENST00000423776.1 linkuse as main transcript	n.91-8T>A	splice_region_variant, intron_variant	1	ENSP00000416620.1	F2Z2M6

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68944

AN:

151994

Hom.:

18845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.533

AC:

78072

AN:

146468

Hom.:

21809

AF XY:

0.534

AC XY:

42192

AN XY:

78994

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.461

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.580

AC:

810314

AN:

1396504

Hom.:

241204

Cov.:

AF XY:

0.577

AC XY:

397477

AN XY:

688844

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.529

Gnomad4 ASJ exome

AF:

0.632

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.453

AC:

68949

AN:

152112

Hom.:

18845

Cov.:

AF XY:

0.452

AC XY:

33628

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.516

Gnomad4 ASJ

AF:

0.650

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.558

Hom.:

7526

Bravo

AF:

0.435

Asia WGS

AF:

0.411

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.1

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.066

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over