chr7-30654159-C-T

Variant names:

• chr7-30654159-C-T
• rs4722999
• NM_001883.5:c.1096-559G>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.1096-559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,142 control chromosomes in the GnomAD database, including 33,681 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 0.66 (33681 hom., cov: 33)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001883.5	MANE Select	c.1096-559G>A		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.1177-559G>A		intron	N/A	NP_001189404.1	Q13324-2
	CRHR2	NM_001202482.2		c.1093-559G>A		intron	N/A	NP_001189411.1	Q13324-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000471646.6	TSL:1 MANE Select	c.1096-559G>A		intron	N/A	ENSP00000418722.1	Q13324-1
	CRHR2	ENST00000348438.8	TSL:1	c.1177-559G>A		intron	N/A	ENSP00000340943.4	Q13324-2
	CRHR2	ENST00000506074.6	TSL:1	c.*42+539G>A		intron	N/A	ENSP00000426498.3	Q13324-4

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100665 AN: 152024 Hom.: 33650 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.662 AC: 100744 AN: 152142 Hom.: 33681 Cov.: 33 AF XY: 0.654 AC XY: 48670 AN XY: 74378

African (AFR) AF: 0.690 AC: 28651 AN: 41508

American (AMR) AF: 0.617 AC: 9444 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2519 AN: 5166

South Asian (SAS) AF: 0.426 AC: 2052 AN: 4818

European-Finnish (FIN) AF: 0.656 AC: 6936 AN: 10580

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.682 AC: 46396 AN: 67990

Other (OTH) AF: 0.655 AC: 1383 AN: 2112

Alfa AF: 0.679 Hom.: 5702

Bravo AF: 0.662

Asia WGS AF: 0.460 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.061
DANN	Benign	0.32
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4722999; hg19: chr7-30693775;