rs4723000

Positions:

• chr7-30662298-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.698-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,500,032 control chromosomes in the GnomAD database, including 14,242 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 0.15 (1939 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12303 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.698-82C>T		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.698-82C>T		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22906 AN: 152026 Hom.: 1928 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.130 AC: 175826 AN: 1347888 Hom.: 12303 AF XY: 0.132 AC XY: 89474 AN XY: 676204

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.0980

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0728

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.151 AC: 22948 AN: 152144 Hom.: 1939 Cov.: 33 AF XY: 0.149 AC XY: 11063 AN XY: 74380

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.172

Alfa AF: 0.143 Hom.: 359

Bravo AF: 0.158

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.18

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

LitVar

Other links and lift over

dbSNP: rs4723000; hg19: chr7-30701914;