rs2284217

Variant names:

• chr7-30673992-A-G
• rs2284217
• NM_001883.5:c.230-6679T>C

Variant summary

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

The NM_001883.5(CRHR2):​c.230-6679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,962 control chromosomes in the GnomAD database, including 40,574 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 0.73 (40574 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 24 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.230-6679T>C		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.230-6679T>C		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110449 AN: 151844 Hom.: 40550 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.727 AC: 110515 AN: 151962 Hom.: 40574 Cov.: 31 AF XY: 0.721 AC XY: 53553 AN XY: 74250

African (AFR) AF: 0.651 AC: 26960 AN: 41418

American (AMR) AF: 0.710 AC: 10841 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3190 AN: 5158

South Asian (SAS) AF: 0.682 AC: 3271 AN: 4796

European-Finnish (FIN) AF: 0.711 AC: 7512 AN: 10560

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53269 AN: 67974

Other (OTH) AF: 0.759 AC: 1601 AN: 2108

Alfa AF: 0.763 Hom.: 9081

Bravo AF: 0.725

Asia WGS AF: 0.673 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		0.61
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: rs2284217; hg19: chr7-30713608;