17-45821002-A-G

Variant names:

• chr17-45821002-A-G
• rs242937
• NM_004382.5:c.242-353A>G

Variant summary

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

The NM_004382.5(CRHR1):​c.242-353A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,716 control chromosomes in the GnomAD database, including 24,613 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 0.56 (24613 hom., cov: 34)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 8 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 = 0.845 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.242-353A>G		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.242-353A>G		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.242-353A>G		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.242-353A>G		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.242-353A>G		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.242-353A>G		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84858 AN: 151600 Hom.: 24606 Cov.: 34

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.560 AC: 84886 AN: 151716 Hom.: 24613 Cov.: 34 AF XY: 0.572 AC XY: 42413 AN XY: 74182

African (AFR) AF: 0.433 AC: 17946 AN: 41398

American (AMR) AF: 0.617 AC: 9402 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1853 AN: 3452

East Asian (EAS) AF: 0.866 AC: 4485 AN: 5180

South Asian (SAS) AF: 0.781 AC: 3766 AN: 4820

European-Finnish (FIN) AF: 0.705 AC: 7458 AN: 10572

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.563 AC: 38132 AN: 67746

Other (OTH) AF: 0.545 AC: 1144 AN: 2100

Alfa AF: 0.553 Hom.: 4596

Bravo AF: 0.544

Asia WGS AF: 0.780 AC: 2712 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	1.1
DANN	Benign	0.43
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs242937; hg19: chr17-43898368; COSMIC: COSV53283902; COSMIC: COSV53283902;