rs9892359

Positions:

• chr17-45793325-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.33+8748A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,178 control chromosomes in the GnomAD database, including 2,696 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 (2696 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.33+8748A>G		intron_variant		ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.-492-13685A>G		intron_variant			NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.33+8748A>G		intron_variant		1	NM_004382.5	ENSP00000326060	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24419 AN: 152060 Hom.: 2681 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.161 AC: 24476 AN: 152178 Hom.: 2696 Cov.: 33 AF XY: 0.158 AC XY: 11768 AN XY: 74410

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.158

Alfa AF: 0.122 Hom.: 888

Bravo AF: 0.166

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.78

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: rs9892359; hg19: chr17-43870691;