rs151248954

Variant names:

• chr7-30653597-G-A
• rs151248954
• NM_001883.5:c.1099C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30653597-G-A
• chr7-30653597-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001883.5(CRHR2):​c.1099C>T​(p.Arg367Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,608,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: CRHR2 NM_001883.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.07
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1099C>T	p.Arg367Cys	missense	Exon 12 of 12	NP_001874.2
	CRHR2	NM_001202475.1		c.1180C>T	p.Arg394Cys	missense	Exon 13 of 13	NP_001189404.1	Q13324-2
	CRHR2	NM_001202482.2		c.1096C>T	p.Arg366Cys	missense	Exon 12 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.1099C>T	p.Arg367Cys	missense	Exon 12 of 12	ENSP00000418722.1	Q13324-1
	CRHR2	ENST00000348438.8	TSL:1	c.1180C>T	p.Arg394Cys	missense	Exon 13 of 13	ENSP00000340943.4	Q13324-2
	CRHR2	ENST00000506074.6	TSL:1	c.*46C>T		3_prime_UTR	Exon 13 of 13	ENSP00000426498.3	Q13324-4

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152026 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000740 AC: 18 AN: 243110 AF XY: 0.0000835

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.0000357 AC: 52 AN: 1456804 Hom.: 0 Cov.: 30 AF XY: 0.0000414 AC XY: 30 AN XY: 724804

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.000179 AC: 8 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 86006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111028

Other (OTH) AF: 0.0000830 AC: 5 AN: 60272

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74382

African (AFR) AF: 0.0000241 AC: 1 AN: 41498

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67970

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.28
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		8.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.88
MPC		1.0
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.66
gMVP		0.80
Mutation Taster		=18/82	disease causing

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: rs151248954; hg19: chr7-30693213;