rs4792888

Variant names:

• chr17-45800588-A-G
• rs4792888
• NM_004382.5:c.34-6422A>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.34-6422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,296 control chromosomes in the GnomAD database, including 2,997 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 0.16 (2997 hom., cov: 33)
  • Exomes 𝑓: 0.059 (0 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.34-6422A>G		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.34-6422A>G		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.34-6422A>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.34-6422A>G		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.34-6422A>G		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.34-6422A>G		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24192 AN: 152144 Hom.: 2978 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0588 AC: 2 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 1 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.0417 AC: 1 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.159 AC: 24268 AN: 152262 Hom.: 2997 Cov.: 33 AF XY: 0.156 AC XY: 11605 AN XY: 74466

African (AFR) AF: 0.346 AC: 14376 AN: 41526

American (AMR) AF: 0.0905 AC: 1385 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0292 AC: 141 AN: 4832

European-Finnish (FIN) AF: 0.0904 AC: 960 AN: 10616

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0967 AC: 6577 AN: 68008

Other (OTH) AF: 0.149 AC: 315 AN: 2114

Alfa AF: 0.121 Hom.: 453

Bravo AF: 0.168

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.75
PhyloP100		-1.0
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: rs4792888; hg19: chr17-43877954;