rs17763104

chr17-45828429-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):c.328-786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 152,302 control chromosomes in the GnomAD database, including 771 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 0.090 (771 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.328-786G>A		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-198-786G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.328-786G>A		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.775-515C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13741 AN: 152184 Hom.: 770 Cov.: 33

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0841

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

GnomAD4 genome AF: 0.0902 AC: 13743 AN: 152302 Hom.: 771 Cov.: 33 AF XY: 0.0855 AC XY: 6370 AN XY: 74478

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.0751

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.119 Hom.: 782

Bravo AF: 0.0872

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	-0.83
Cadd	Benign	6.9
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs17763104; hg19: chr17-43905795;