rs8192498

Variant names:

• chr7-30662196-C-A
• rs8192498
• NM_001883.5:c.718G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30662196-C-A
• chr7-30662196-C-T

Variant summary

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

The NM_001883.5(CRHR2):​c.718G>T​(p.Val240Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRHR2 NM_001883.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.718G>T	p.Val240Phe	missense_variant	Exon 7 of 12	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.718G>T	p.Val240Phe	missense_variant	Exon 7 of 12	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.1
DANN	Benign	0.95
DEOGEN2	Benign	0.16	.;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;L;.
PhyloP100		-0.99
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.075	T;T;T;T
Sift4G	Benign	0.083	T;T;T;T
Polyphen		0.050, 0.0070, 0.014	.;B;B;B
Vest4		0.74
MutPred		0.56		Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);.;
MVP		0.25
MPC		0.56
ClinPred		0.23	T
GERP RS		1.3
Varity_R		0.35
gMVP		0.76
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8192498; hg19: chr7-30701812;