7-30674717-C-T

Variant names:

• chr7-30674717-C-T
• rs2284218
• NM_001883.5:c.229+7198G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.229+7198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,986 control chromosomes in the GnomAD database, including 20,450 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 0.48 (20450 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 16 publications found

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]

ENSG00000305335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.229+7198G>A		intron_variant	Intron 2 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.229+7198G>A		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73415 AN: 151868 Hom.: 20450 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.483 AC: 73421 AN: 151986 Hom.: 20450 Cov.: 31 AF XY: 0.481 AC XY: 35685 AN XY: 74252

African (AFR) AF: 0.189 AC: 7838 AN: 41482

American (AMR) AF: 0.541 AC: 8269 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2446 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2300 AN: 5128

South Asian (SAS) AF: 0.453 AC: 2177 AN: 4810

European-Finnish (FIN) AF: 0.580 AC: 6130 AN: 10574

Middle Eastern (MID) AF: 0.583 AC: 169 AN: 290

European-Non Finnish (NFE) AF: 0.625 AC: 42470 AN: 67930

Other (OTH) AF: 0.528 AC: 1117 AN: 2114

Alfa AF: 0.581 Hom.: 99958

Bravo AF: 0.468

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.23
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284218; hg19: chr7-30714333;