rs17689918

Positions:

• chr17-45832722-G-A
• chr17-45832722-G-T

Variant summary

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

The NM_004382.5(CRHR1):​c.771-416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,248 control chromosomes in the GnomAD database, including 2,151 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 0.15 (2151 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.771-416G>A		intron_variant		ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.246-416G>A		intron_variant			NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.771-416G>A		intron_variant		1	NM_004382.5	ENSP00000326060	P1
MAPT-AS1	ENST00000634876.2	n.604-3361C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22270 AN: 152130 Hom.: 2153 Cov.: 33

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.146 AC: 22262 AN: 152248 Hom.: 2151 Cov.: 33 AF XY: 0.137 AC XY: 10213 AN XY: 74446

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.186

Alfa AF: 0.195 Hom.: 1284

Bravo AF: 0.152

Asia WGS AF: 0.0330 AC: 116 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	5.0
DANN	Benign	0.51

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: rs17689918; hg19: chr17-43910088;