chr7-30669859-C-A

Variant names:

• chr7-30669859-C-A
• rs2190242
• NM_001883.5:c.230-2546G>T

Variant summary

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

The NM_001883.5(CRHR2):​c.230-2546G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,062 control chromosomes in the GnomAD database, including 46,150 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 0.78 (46150 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 35 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.230-2546G>T		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.230-2546G>T		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117770 AN: 151944 Hom.: 46107 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.775 AC: 117864 AN: 152062 Hom.: 46150 Cov.: 31 AF XY: 0.768 AC XY: 57110 AN XY: 74330

African (AFR) AF: 0.829 AC: 34364 AN: 41462

American (AMR) AF: 0.779 AC: 11907 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2745 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2348 AN: 5144

South Asian (SAS) AF: 0.536 AC: 2576 AN: 4810

European-Finnish (FIN) AF: 0.778 AC: 8222 AN: 10572

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53118 AN: 67986

Other (OTH) AF: 0.762 AC: 1613 AN: 2116

Alfa AF: 0.774 Hom.: 137091

Bravo AF: 0.780

Asia WGS AF: 0.504 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-0.27
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: rs2190242; hg19: chr7-30709475;