chr17-45817432-G-C

Variant names:

• chr17-45817432-G-C
• rs81189
• NM_004382.5:c.241+850G>C

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+850G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,020 control chromosomes in the GnomAD database, including 18,455 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 0.48 (18455 hom., cov: 32)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	NM_004382.5	MANE Select	c.241+850G>C		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.241+850G>C		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.241+850G>C		intron	N/A	NP_001138620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.241+850G>C		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.241+850G>C		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.241+850G>C		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72503 AN: 151902 Hom.: 18450 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.477 AC: 72520 AN: 152020 Hom.: 18455 Cov.: 32 AF XY: 0.494 AC XY: 36696 AN XY: 74322

African (AFR) AF: 0.345 AC: 14283 AN: 41458

American (AMR) AF: 0.554 AC: 8469 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3466

East Asian (EAS) AF: 0.862 AC: 4452 AN: 5162

South Asian (SAS) AF: 0.686 AC: 3313 AN: 4826

European-Finnish (FIN) AF: 0.666 AC: 7035 AN: 10568

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31797 AN: 67948

Other (OTH) AF: 0.471 AC: 989 AN: 2100

Alfa AF: 0.335 Hom.: 930

Bravo AF: 0.463

Asia WGS AF: 0.733 AC: 2548 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		-0.95
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: rs81189; hg19: chr17-43894798;