chr17-45802681-G-A

Position:

• chr17-45802681-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004382.5(CRHR1):​c.34-4329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,990 control chromosomes in the GnomAD database, including 16,858 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 0.45 (16858 hom., cov: 32)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.34-4329G>A		intron_variant		ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.-492-4329G>A		intron_variant			NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.34-4329G>A		intron_variant		1	NM_004382.5	ENSP00000326060	P1
MAPT-AS1	ENST00000634876.2	n.2594-1891C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68615 AN: 151872 Hom.: 16854 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.452 AC: 68631 AN: 151990 Hom.: 16858 Cov.: 32 AF XY: 0.468 AC XY: 34781 AN XY: 74296

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.449

Alfa AF: 0.440 Hom.: 28129

Bravo AF: 0.438

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Benign	0.77

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: rs110402; hg19: chr17-43880047;