17-45818213-C-T

Variant names:

• chr17-45818213-C-T
• rs242939
• NM_004382.5:c.241+1631C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.241+1631C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,212 control chromosomes in the GnomAD database, including 58,232 homozygotes. 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 0.87 (58232 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 72 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004382.5. 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
	CRHR1	NM_004382.5	MANE Select	c.241+1631C>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.241+1631C>T		intron	N/A	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.241+1631C>T		intron	N/A	NP_001138620.1	P34998-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.241+1631C>T		intron	N/A	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.241+1631C>T		intron	N/A	ENSP00000381333.3	P34998-1
	CRHR1	ENST00000577353.5	TSL:1	c.241+1631C>T		intron	N/A	ENSP00000462016.1	P34998-4

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132010 AN: 152094 Hom.: 58223 Cov.: 33

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.883

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.868 AC: 132060 AN: 152212 Hom.: 58232 Cov.: 33 AF XY: 0.871 AC XY: 64871 AN XY: 74438

African (AFR) AF: 0.690 AC: 28631 AN: 41488

American (AMR) AF: 0.927 AC: 14187 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3155 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5162

South Asian (SAS) AF: 0.974 AC: 4708 AN: 4832

European-Finnish (FIN) AF: 0.951 AC: 10101 AN: 10618

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63142 AN: 68014

Other (OTH) AF: 0.884 AC: 1865 AN: 2110

Alfa AF: 0.914 Hom.: 172788

Bravo AF: 0.858

Asia WGS AF: 0.966 AC: 3361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.75
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs242939;

hg19: chr17-43895579;