NM_001883.5:c.230-5305T>G

Variant names:

• chr7-30672618-A-C
• rs2267712
• NM_001883.5:c.230-5305T>G

Variant summary

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

The NM_001883.5(CRHR2):​c.230-5305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,186 control chromosomes in the GnomAD database, including 53,107 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 0.83 (53107 hom., cov: 33)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 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.230-5305T>G		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.311-5305T>G		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.230-5305T>G		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.230-5305T>G		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.311-5305T>G		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.230-5305T>G		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126813 AN: 152066 Hom.: 53056 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.834 AC: 126920 AN: 152186 Hom.: 53107 Cov.: 33 AF XY: 0.828 AC XY: 61608 AN XY: 74410

African (AFR) AF: 0.839 AC: 34852 AN: 41526

American (AMR) AF: 0.840 AC: 12850 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3070 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3199 AN: 5158

South Asian (SAS) AF: 0.731 AC: 3524 AN: 4818

European-Finnish (FIN) AF: 0.802 AC: 8498 AN: 10592

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58094 AN: 68002

Other (OTH) AF: 0.849 AC: 1793 AN: 2112

Alfa AF: 0.843 Hom.: 8525

Bravo AF: 0.839

Asia WGS AF: 0.719 AC: 2503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-1.4
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: rs2267712; hg19: chr7-30712234;