7-30674820-A-G

Variant names:

• chr7-30674820-A-G
• rs2284219
• NM_001883.5:c.229+7095T>C

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+7095T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,932 control chromosomes in the GnomAD database, including 20,471 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 (20471 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.229+7095T>C		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+7095T>C		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73493 AN: 151812 Hom.: 20471 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.484 AC: 73500 AN: 151932 Hom.: 20471 Cov.: 31 AF XY: 0.481 AC XY: 35719 AN XY: 74218

African (AFR) AF: 0.190 AC: 7876 AN: 41480

American (AMR) AF: 0.542 AC: 8279 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2445 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2317 AN: 5126

South Asian (SAS) AF: 0.454 AC: 2180 AN: 4804

European-Finnish (FIN) AF: 0.580 AC: 6136 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42475 AN: 67886

Other (OTH) AF: 0.530 AC: 1118 AN: 2110

Alfa AF: 0.493 Hom.: 8587

Bravo AF: 0.468

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.56
PhyloP100		-1.6
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: rs2284219; hg19: chr7-30714436;