rs4792888

Positions:

• chr17-45800588-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.34-6422A>G		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-492-6422A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.34-6422A>G		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.2796T>C		non_coding_transcript_exon_variant	6/7	5

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

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0417

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

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.149

Alfa AF: 0.131 Hom.: 325

Bravo AF: 0.168

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs4792888; hg19: chr17-43877954;