rs7812133

Positions:

• chr7-30655790-G-A

Variant summary

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

The NM_001883.5(CRHR2):​c.918-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,591,760 control chromosomes in the GnomAD database, including 3,875 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 0.10 (1611 hom., cov: 33)
  • Exomes 𝑓: 0.040 (2264 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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]

LOC124901609 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.918-75C>T		intron_variant		ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.918-75C>T		intron_variant		1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15201 AN: 152052 Hom.: 1600 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0843

GnomAD4 exome AF: 0.0399 AC: 57488 AN: 1439592 Hom.: 2264 Cov.: 31 AF XY: 0.0383 AC XY: 27366 AN XY: 713966

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.0410

Gnomad4 ASJ exome AF: 0.0284

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.00843

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0504

GnomAD4 genome AF: 0.100 AC: 15237 AN: 152168 Hom.: 1611 Cov.: 33 AF XY: 0.0965 AC XY: 7181 AN XY: 74402

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0834

Alfa AF: 0.0805 Hom.: 204

Bravo AF: 0.113

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.53

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: rs7812133; hg19: chr7-30695406;