rs41280114

Variant names:

• chr17-45821400-G-A
• rs41280114
• NM_004382.5:c.287G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45821400-G-A
• chr17-45821400-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004382.5(CRHR1):​c.287G>A​(p.Arg96His) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: CRHR1 NM_004382.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

LINC02210-CRHR1 (HGNC:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.409694).
• BS2: High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.287G>A	p.Arg96His	missense_variant	Exon 4 of 13	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.287G>A	p.Arg96His	missense_variant	Exon 4 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540	c.-239G>A		5_prime_UTR_variant	Exon 6 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248546 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000954

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1460980 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726802

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33480

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.0000232 AC: 2 AN: 86258

Gnomad4 FIN exome AF: 0.0000381 AC: 2 AN: 52532

Gnomad4 NFE exome AF: 0.0000324 AC: 36 AN: 1112000

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152238 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74388

Gnomad4 AFR AF: 0.0000241 AC: 0.0000241173 AN: 0.0000241173

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206697 AN: 0.000206697

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000294 AC: 0.0000293953 AN: 0.0000293953

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.4	.;L;.;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.050	.;N;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.18	.;T;T;.;T
Sift4G	Uncertain	0.018	D;T;T;D;T
Polyphen		1.0, 0.99	.;D;D;D;D
Vest4		0.47
MutPred		0.70		Loss of stability (P = 0.1466);Loss of stability (P = 0.1466);.;Loss of stability (P = 0.1466);Loss of stability (P = 0.1466);
MVP		0.57
MPC		1.6
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.73
gMVP		0.68
Mutation Taster		=33/67	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

Publications

LitVar

Other links and lift over

dbSNP: rs41280114; hg19: chr17-43898766;