7-30676471-G-A

Variant names:

• chr7-30676471-G-A
• rs2267715
• NM_001883.5:c.229+5444C>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+5444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,900 control chromosomes in the GnomAD database, including 20,419 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 (20419 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 19 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 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+5444C>T		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.310+5444C>T		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.229+5444C>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+5444C>T		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.310+5444C>T		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.229+5444C>T		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73280 AN: 151782 Hom.: 20419 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.482 AC: 73285 AN: 151900 Hom.: 20419 Cov.: 31 AF XY: 0.480 AC XY: 35608 AN XY: 74230

African (AFR) AF: 0.186 AC: 7708 AN: 41408

American (AMR) AF: 0.541 AC: 8268 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2443 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2288 AN: 5140

South Asian (SAS) AF: 0.454 AC: 2182 AN: 4810

European-Finnish (FIN) AF: 0.579 AC: 6111 AN: 10550

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.626 AC: 42492 AN: 67928

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.556 Hom.: 47649

Bravo AF: 0.467

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.61
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: rs2267715; hg19: chr7-30716087;