chr7-30665489-G-A

Position:

• chr7-30665489-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.425+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,465,310 control chromosomes in the GnomAD database, including 339,123 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 0.62 (30174 hom., cov: 32)
  • Exomes 𝑓: 0.68 (308949 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.425+41C>T		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.425+41C>T		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94043 AN: 151958 Hom.: 30160 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.627

GnomAD3 exomes AF: 0.647 AC: 100711 AN: 155606 Hom.: 33523 AF XY: 0.641 AC XY: 52325 AN XY: 81626

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.727

Gnomad ASJ exome AF: 0.716

Gnomad EAS exome AF: 0.482

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.666

GnomAD4 exome AF: 0.681 AC: 894087 AN: 1313234 Hom.: 308949 Cov.: 20 AF XY: 0.676 AC XY: 440504 AN XY: 651948

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.619 AC: 94087 AN: 152076 Hom.: 30174 Cov.: 32 AF XY: 0.617 AC XY: 45840 AN XY: 74304

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.623

Alfa AF: 0.682 Hom.: 9405

Bravo AF: 0.610

Asia WGS AF: 0.467 AC: 1624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.87

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: rs8192496; hg19: chr7-30705105; COSMIC: COSV59267639;