rs2190242

chr7-30669859-C-Achr7-30669859-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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/exons	MANE	UniProt
CRHR2	NM_001883.5	c.230-2546G>T		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.230-2546G>T		intron_variant		1	NM_001883.5	P1

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

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.762

Alfa AF: 0.771 Hom.: 58639

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

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: rs2190242; hg19: chr7-30709475;