17-45825578-C-T

Variant names:

• chr17-45825578-C-T
• rs1912151
• NM_004382.5:c.328-3637C>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.328-3637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 154,632 control chromosomes in the GnomAD database, including 2,190 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 0.14 (2142 hom., cov: 33)
  • Exomes 𝑓: 0.19 (48 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 36 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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.328-3637C>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.328-3637C>T		intron	N/A	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.328-3637C>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.328-3637C>T		intron	N/A	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.328-3637C>T		intron	N/A	ENSP00000381333.3	P34998-1
	CRHR1	ENST00000577353.5	TSL:1	c.328-3637C>T		intron	N/A	ENSP00000462016.1	P34998-4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21855 AN: 152200 Hom.: 2144 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.252 AC: 113 AN: 448 AF XY: 0.226

Gnomad AFR exome AF: 0.167

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0556

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.191 AC: 443 AN: 2314 Hom.: 48 Cov.: 0 AF XY: 0.204 AC XY: 243 AN XY: 1194

African (AFR) AF: 0.0875 AC: 7 AN: 80

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.106 AC: 10 AN: 94

European-Finnish (FIN) AF: 0.125 AC: 2 AN: 16

Middle Eastern (MID) AF: 0.205 AC: 335 AN: 1632

European-Non Finnish (NFE) AF: 0.226 AC: 62 AN: 274

Other (OTH) AF: 0.127 AC: 26 AN: 204

GnomAD4 genome AF: 0.143 AC: 21845 AN: 152318 Hom.: 2142 Cov.: 33 AF XY: 0.134 AC XY: 10002 AN XY: 74484

African (AFR) AF: 0.0430 AC: 1787 AN: 41580

American (AMR) AF: 0.176 AC: 2689 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4832

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10620

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14773 AN: 68004

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.172 Hom.: 1783

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.62
PhyloP100		0.28
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: rs1912151; hg19: chr17-43902944;