rs2284216

Variant names:

• chr7-30672345-G-T
• rs2284216
• NM_001883.5:c.230-5032C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.230-5032C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,240 control chromosomes in the GnomAD database, including 1,238 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 0.12 (1238 hom., cov: 33)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 9 publications found

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]

ENSG00000305335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.230-5032C>A		intron_variant	Intron 2 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.230-5032C>A		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18226 AN: 152122 Hom.: 1229 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18258 AN: 152240 Hom.: 1238 Cov.: 33 AF XY: 0.120 AC XY: 8964 AN XY: 74462

African (AFR) AF: 0.181 AC: 7531 AN: 41520

American (AMR) AF: 0.0925 AC: 1414 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3472

East Asian (EAS) AF: 0.167 AC: 866 AN: 5180

South Asian (SAS) AF: 0.201 AC: 968 AN: 4824

European-Finnish (FIN) AF: 0.0695 AC: 738 AN: 10618

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6021 AN: 68018

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.102 Hom.: 3635

Bravo AF: 0.124

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.55
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284216; hg19: chr7-30711961;