17-45833287-T-C

Variant names:

• chr17-45833287-T-C
• rs242950
• NM_004382.5:c.843+77T>C

Variant summary

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

The NM_001145146.2(CRHR1):​c.930+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 1,521,158 control chromosomes in the GnomAD database, including 622,042 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 0.88 (59345 hom., cov: 30)
  • Exomes 𝑓: 0.91 (562697 hom.)
• Consequence: CRHR1 NM_001145146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 9 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=-0.91).
• 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_001145146.2. 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.843+77T>C		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.930+77T>C		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.843+77T>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.843+77T>C		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.930+77T>C		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.843+77T>C		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134006 AN: 151912 Hom.: 59313 Cov.: 30

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.877

GnomAD4 exome AF: 0.906 AC: 1240292 AN: 1369128 Hom.: 562697 Cov.: 22 AF XY: 0.908 AC XY: 623078 AN XY: 686382

African (AFR) AF: 0.807 AC: 25535 AN: 31652

American (AMR) AF: 0.943 AC: 42033 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 22938 AN: 25498

East Asian (EAS) AF: 1.00 AC: 39262 AN: 39270

South Asian (SAS) AF: 0.967 AC: 81602 AN: 84402

European-Finnish (FIN) AF: 0.920 AC: 48723 AN: 52932

Middle Eastern (MID) AF: 0.898 AC: 4989 AN: 5558

European-Non Finnish (NFE) AF: 0.898 AC: 923145 AN: 1027922

Other (OTH) AF: 0.908 AC: 52065 AN: 57322

GnomAD4 genome AF: 0.882 AC: 134090 AN: 152030 Hom.: 59345 Cov.: 30 AF XY: 0.887 AC XY: 65872 AN XY: 74304

African (AFR) AF: 0.814 AC: 33717 AN: 41434

American (AMR) AF: 0.922 AC: 14100 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5134 AN: 5136

South Asian (SAS) AF: 0.971 AC: 4666 AN: 4804

European-Finnish (FIN) AF: 0.923 AC: 9786 AN: 10602

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60628 AN: 67980

Other (OTH) AF: 0.878 AC: 1855 AN: 2112

Alfa AF: 0.881 Hom.: 7386

Bravo AF: 0.880

Asia WGS AF: 0.971 AC: 3378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		-0.23
PromoterAI		0.022	Neutral
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: rs242950; hg19: chr17-43910653;