chr17-45829613-G-A

Variant names:

• chr17-45829613-G-A
• rs542050010
• ENST00000398285.7:c.487G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004382.5(CRHR1):​c.434+292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,550,890 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 2 publications found

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119228244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.434+292G>A		intron_variant	Intron 5 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.434+292G>A		intron_variant	Intron 5 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-92+292G>A		intron_variant	Intron 7 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398754 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689922

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.0000409 AC: 2 AN: 48856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078880

Other (OTH) AF: 0.00 AC: 0 AN: 57988

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.8
DANN	Benign	0.89
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
PhyloP100		-0.084
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.10	.;N
REVEL	Benign	0.029
Sift	Uncertain	0.019	.;D
Sift4G	Uncertain	0.052	T;D
Polyphen		0.0060	.;B
Vest4		0.086
MutPred		0.44		Gain of phosphorylation at A163 (P = 0.0736);Gain of phosphorylation at A163 (P = 0.0736);
MVP		0.65
MPC		1.1
ClinPred		0.13	T
GERP RS		0.90
Varity_R		0.020
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs542050010; hg19: chr17-43906979;