rs2267710

Positions:

• chr7-30656574-C-T

Variant summary

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

The NM_001883.5(CRHR2):​c.832-562G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,090 control chromosomes in the GnomAD database, including 33,626 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 0.66 (33626 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.832-562G>A		intron_variant		ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.832-562G>A		intron_variant		1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100527 AN: 151970 Hom.: 33593 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.662 AC: 100608 AN: 152090 Hom.: 33626 Cov.: 32 AF XY: 0.654 AC XY: 48609 AN XY: 74360

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.653

Alfa AF: 0.675 Hom.: 33793

Bravo AF: 0.661

Asia WGS AF: 0.454 AC: 1580 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.45

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: rs2267710; hg19: chr7-30696190;