7-30678487-G-A

Variant names:

• chr7-30678487-G-A
• rs2284220
• NM_001883.5:c.229+3428C>T

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+3428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,202 control chromosomes in the GnomAD database, including 54,039 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 0.84 (54039 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001883.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001883.5	MANE Select	c.229+3428C>T		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.310+3428C>T		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.229+3428C>T		intron	N/A	NP_001189411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000471646.6	TSL:1 MANE Select	c.229+3428C>T		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.310+3428C>T		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.229+3428C>T		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127889 AN: 152082 Hom.: 53998 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.841 AC: 127982 AN: 152202 Hom.: 54039 Cov.: 32 AF XY: 0.835 AC XY: 62097 AN XY: 74400

African (AFR) AF: 0.864 AC: 35886 AN: 41530

American (AMR) AF: 0.843 AC: 12891 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3167 AN: 5154

South Asian (SAS) AF: 0.733 AC: 3540 AN: 4828

European-Finnish (FIN) AF: 0.802 AC: 8503 AN: 10598

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58085 AN: 68012

Other (OTH) AF: 0.852 AC: 1799 AN: 2112

Alfa AF: 0.848 Hom.: 108888

Bravo AF: 0.847

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-0.40
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: rs2284220; hg19: chr7-30718103;