NM_001883.5:c.229+5958G>A

Variant names:

• chr7-30675957-C-T
• rs2014663
• NM_001883.5:c.229+5958G>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+5958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,232 control chromosomes in the GnomAD database, including 58,242 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 0.87 (58242 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 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+5958G>A		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.310+5958G>A		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.229+5958G>A		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+5958G>A		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.310+5958G>A		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.229+5958G>A		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132483 AN: 152114 Hom.: 58184 Cov.: 32

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.871 AC: 132600 AN: 152232 Hom.: 58242 Cov.: 32 AF XY: 0.864 AC XY: 64282 AN XY: 74422

African (AFR) AF: 0.969 AC: 40275 AN: 41566

American (AMR) AF: 0.856 AC: 13094 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3068 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3176 AN: 5166

South Asian (SAS) AF: 0.732 AC: 3521 AN: 4812

European-Finnish (FIN) AF: 0.802 AC: 8495 AN: 10588

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.854 AC: 58081 AN: 68014

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.861 Hom.: 167140

Bravo AF: 0.881

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.24
DANN	Benign	0.32
PhyloP100		-0.78
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: rs2014663; hg19: chr7-30715573;