rs255097

chr7-30687343-G-Achr7-30687343-G-Cchr7-30687343-G-T

Variant summary

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

The ENST00000348438.8(CRHR2):c.184+1848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,804 control chromosomes in the GnomAD database, including 19,225 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 0.47 (19225 hom., cov: 30)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001202475.1	c.184+1848C>T		intron_variant
CRHR2	NM_001202481.1	c.-166-728C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000348438.8	c.184+1848C>T		intron_variant		1
CRHR2	ENST00000445981.5	c.184+1848C>T		intron_variant		1
CRHR2	ENST00000423776.1	c.185-728C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70908 AN: 151686 Hom.: 19224 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.467 AC: 70915 AN: 151804 Hom.: 19225 Cov.: 30 AF XY: 0.465 AC XY: 34507 AN XY: 74158

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.506

Alfa AF: 0.416 Hom.: 1743

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.0
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs255097; hg19: chr7-30726959;