7-30688836-C-T

Position:

• chr7-30688836-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000348438.8(CRHR2):​c.184+355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 466,224 control chromosomes in the GnomAD database, including 26,213 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 0.37 (14656 hom., cov: 34)
  • Exomes 𝑓: 0.25 (11557 hom.)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001202475.1	c.184+355G>A		intron_variant
CRHR2	NM_001202481.1	c.-167+355G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000348438.8	c.184+355G>A		intron_variant		1
CRHR2	ENST00000445981.5	c.184+355G>A		intron_variant		1
CRHR2	ENST00000462882.1	n.453G>A		non_coding_transcript_exon_variant	3/4	1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56931 AN: 151980 Hom.: 14618 Cov.: 34

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.338

GnomAD3 exomes AF: 0.265 AC: 35472 AN: 133778 Hom.: 5773 AF XY: 0.258 AC XY: 18794 AN XY: 72846

Gnomad AFR exome AF: 0.762

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.156

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.253 AC: 79616 AN: 314126 Hom.: 11557 Cov.: 0 AF XY: 0.252 AC XY: 44849 AN XY: 178120

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.375 AC: 57032 AN: 152098 Hom.: 14656 Cov.: 34 AF XY: 0.369 AC XY: 27431 AN XY: 74392

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.339

Alfa AF: 0.306 Hom.: 2660

Bravo AF: 0.402

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs917195; hg19: chr7-30728452; COSMIC: COSV59264279;