7-30673085-C-G

Position:

• chr7-30673085-C-G

Variant summary

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

The NM_001883.5(CRHR2):​c.230-5772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,134 control chromosomes in the GnomAD database, including 21,947 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 0.50 (21947 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.230-5772G>C		intron_variant		ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.230-5772G>C		intron_variant		1	NM_001883.5	ENSP00000418722	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75907 AN: 152014 Hom.: 21949 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.499 AC: 75911 AN: 152134 Hom.: 21947 Cov.: 32 AF XY: 0.497 AC XY: 36947 AN XY: 74362

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.538

Alfa AF: 0.442 Hom.: 1468

Bravo AF: 0.479

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.80

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: rs1076292; hg19: chr7-30712701;