17-45808001-G-T

Variant names:

• chr17-45808001-G-T
• rs242924
• NM_004382.5:c.121+904G>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.121+904G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,934 control chromosomes in the GnomAD database, including 16,767 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 0.45 (16767 hom., cov: 31)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 106 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 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.121+904G>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.121+904G>T		intron	N/A	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.121+904G>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.121+904G>T		intron	N/A	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.121+904G>T		intron	N/A	ENSP00000381333.3	P34998-1
	CRHR1	ENST00000577353.5	TSL:1	c.121+904G>T		intron	N/A	ENSP00000462016.1	P34998-4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68137 AN: 151816 Hom.: 16760 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.449 AC: 68154 AN: 151934 Hom.: 16767 Cov.: 31 AF XY: 0.465 AC XY: 34564 AN XY: 74262

African (AFR) AF: 0.300 AC: 12436 AN: 41462

American (AMR) AF: 0.530 AC: 8087 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3466

East Asian (EAS) AF: 0.914 AC: 4711 AN: 5154

South Asian (SAS) AF: 0.701 AC: 3377 AN: 4816

European-Finnish (FIN) AF: 0.624 AC: 6588 AN: 10552

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30035 AN: 67914

Other (OTH) AF: 0.449 AC: 942 AN: 2100

Alfa AF: 0.452 Hom.: 9970

Bravo AF: 0.435

Asia WGS AF: 0.756 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.90
PhyloP100		0.023
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

Other links and lift over

dbSNP: rs242924; hg19: chr17-43885367;