rs765062216

Variant names:

• chr7-30660618-G-C
• rs765062216
• NM_001883.5:c.786C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001883.5(CRHR2):​c.786C>G​(p.Asp262Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,420,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D262N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: CRHR2 NM_001883.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.555
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0820514).

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.786C>G	p.Asp262Glu	missense	Exon 8 of 12	NP_001874.2
	CRHR2	NM_001202475.1		c.867C>G	p.Asp289Glu	missense	Exon 9 of 13	NP_001189404.1	Q13324-2
	CRHR2	NM_001202482.2		c.783C>G	p.Asp261Glu	missense	Exon 8 of 12	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.786C>G	p.Asp262Glu	missense	Exon 8 of 12	ENSP00000418722.1	Q13324-1
	CRHR2	ENST00000348438.8	TSL:1	c.867C>G	p.Asp289Glu	missense	Exon 9 of 13	ENSP00000340943.4	Q13324-2
	CRHR2	ENST00000506074.6	TSL:1	c.786C>G	p.Asp262Glu	missense	Exon 8 of 13	ENSP00000426498.3	Q13324-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000432 AC: 8 AN: 185148 AF XY: 0.0000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000634 AC: 9 AN: 1420184 Hom.: 0 Cov.: 31 AF XY: 0.00000285 AC XY: 2 AN XY: 702294

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.000234 AC: 9 AN: 38468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25344

East Asian (EAS) AF: 0.00 AC: 0 AN: 37738

South Asian (SAS) AF: 0.00 AC: 0 AN: 80684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090508

Other (OTH) AF: 0.00 AC: 0 AN: 58892

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000335 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		-0.56
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.24
MutPred		0.54		Gain of methylation at K258 (P = 0.1072)
MVP		0.38
MPC		0.37
ClinPred		0.029	T
GERP RS		-2.0
Varity_R		0.12
gMVP		0.24
Mutation Taster		=91/9	polymorphism

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: rs765062216; hg19: chr7-30700234;