dbSNP rs917195: CRHR2:n.453G>A (chr7-30688836-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000462882.1(CRHR2):n.453G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 466,224 control chromosomes in the GnomAD database, including 26,213 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 0.37 ( 14656 hom., cov: 34)

Exomes 𝑓: 0.25 ( 11557 hom. )

Consequence

CRHR2
ENST00000462882.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

18 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]

CRHR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001202475.1 link	c.184+355G>A		intron_variant	Intron 2 of 12		NP_001189404.1
CRHR2	NM_001202481.1 link	c.-167+355G>A		intron_variant	Intron 2 of 13		NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
CRHR2	ENST00000462882.1 link	n.453G>A	non_coding_transcript_exon_variant	Exon 3 of 4	1
CRHR2	ENST00000348438.8 link	c.184+355G>A	intron_variant	Intron 2 of 12	1	ENSP00000340943.4
CRHR2	ENST00000445981.5 link	c.184+355G>A	intron_variant	Intron 2 of 2	1	ENSP00000401241.1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56931

AN:

151980

Hom.:

14618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.265

AC:

35472

AN:

133778

AF XY:

0.258

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.253

AC:

79616

AN:

314126

Hom.:

11557

Cov.:

AF XY:

0.252

AC XY:

44849

AN XY:

178120

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.743

AC:

6723

AN:

9050

American (AMR)

AF:

0.287

AC:

7878

AN:

27428

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

2579

AN:

11232

East Asian (EAS)

AF:

0.166

AC:

1661

AN:

9998

South Asian (SAS)

AF:

0.272

AC:

16200

AN:

59664

European-Finnish (FIN)

AF:

0.192

AC:

2535

AN:

13196

Middle Eastern (MID)

AF:

0.293

AC:

834

AN:

2848

European-Non Finnish (NFE)

AF:

0.224

AC:

37194

AN:

165684

Other (OTH)

AF:

0.267

AC:

4012

AN:

15026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.376

Heterozygous variant carriers

3513

7026

10538

14051

17564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.375

AC:

57032

AN:

152098

Hom.:

14656

Cov.:

AF XY:

0.369

AC XY:

27431

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.743

AC:

30785

AN:

41436

American (AMR)

AF:

0.304

AC:

4646

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

751

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

913

AN:

5178

South Asian (SAS)

AF:

0.274

AC:

1319

AN:

4820

European-Finnish (FIN)

AF:

0.189

AC:

2009

AN:

10612

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15515

AN:

67972

Other (OTH)

AF:

0.339

AC:

716

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1506

3012

4519

6025

7531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.306

Hom.:

2660

Bravo

AF:

0.402

Asia WGS

AF:

0.302

AC:

1051

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over