rs2284219

chr7-30674820-A-Gchr7-30674820-A-T

Variant summary

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

The NM_001883.5(CRHR2):c.229+7095T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,932 control chromosomes in the GnomAD database, including 20,471 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 (20471 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.91).
• 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+7095T>C		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.229+7095T>C		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73493 AN: 151812 Hom.: 20471 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.484 AC: 73500 AN: 151932 Hom.: 20471 Cov.: 31 AF XY: 0.481 AC XY: 35719 AN XY: 74218

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.530

Alfa AF: 0.432 Hom.: 1461

Bravo AF: 0.468

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.19
Dann	Benign	0.56

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: rs2284219; hg19: chr7-30714436;