rs242941

chr17-45815154-A-Cchr17-45815154-A-T

Variant summary

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

The NM_004382.5(CRHR1):c.122-1309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,162 control chromosomes in the GnomAD database, including 31,535 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 0.63 (31535 hom., cov: 34)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.122-1309A>C		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-404-1309A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-1309A>C		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.2593+10429T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95257 AN: 152044 Hom.: 31539 Cov.: 34

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.626 AC: 95264 AN: 152162 Hom.: 31535 Cov.: 34 AF XY: 0.633 AC XY: 47097 AN XY: 74370

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.663

Alfa AF: 0.659 Hom.: 9340

Bravo AF: 0.617

Asia WGS AF: 0.791 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.21
Dann	Benign	0.53

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: rs242941; hg19: chr17-43892520;