rs2267715

chr7-30676471-G-Achr7-30676471-G-C

Variant summary

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

The NM_001883.5(CRHR2):c.229+5444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,900 control chromosomes in the GnomAD database, including 20,419 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 0.48 (20419 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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 (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.229+5444C>T		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.229+5444C>T		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73280 AN: 151782 Hom.: 20419 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.482 AC: 73285 AN: 151900 Hom.: 20419 Cov.: 31 AF XY: 0.480 AC XY: 35608 AN XY: 74230

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.529

Alfa AF: 0.549 Hom.: 6511

Bravo AF: 0.467

Asia WGS AF: 0.415 AC: 1442 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	10
Dann	Benign	0.72

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: rs2267715; hg19: chr7-30716087;