chr17-45833089-G-A

Variant names:

• chr17-45833089-G-A
• rs17689966
• NM_004382.5:c.771-49G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.771-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,513,444 control chromosomes in the GnomAD database, including 271,848 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 0.56 (24827 hom., cov: 33)
  • Exomes 𝑓: 0.60 (247021 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 45 publications found

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:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004382.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	NM_004382.5	MANE Select	c.771-49G>A		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.858-49G>A		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.771-49G>A		intron	N/A	NP_001138620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.771-49G>A		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.858-49G>A		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.771-49G>A		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85683 AN: 151948 Hom.: 24823 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.634 AC: 157777 AN: 248734 AF XY: 0.636

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.814

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.598 AC: 813548 AN: 1361378 Hom.: 247021 Cov.: 22 AF XY: 0.602 AC XY: 411005 AN XY: 683066

African (AFR) AF: 0.446 AC: 14154 AN: 31728

American (AMR) AF: 0.705 AC: 31419 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 13462 AN: 25460

East Asian (EAS) AF: 0.819 AC: 32224 AN: 39338

South Asian (SAS) AF: 0.765 AC: 64603 AN: 84480

European-Finnish (FIN) AF: 0.702 AC: 37380 AN: 53280

Middle Eastern (MID) AF: 0.580 AC: 3241 AN: 5592

European-Non Finnish (NFE) AF: 0.572 AC: 582817 AN: 1019742

Other (OTH) AF: 0.599 AC: 34248 AN: 57166

GnomAD4 genome AF: 0.564 AC: 85706 AN: 152066 Hom.: 24827 Cov.: 33 AF XY: 0.576 AC XY: 42794 AN XY: 74350

African (AFR) AF: 0.460 AC: 19067 AN: 41470

American (AMR) AF: 0.615 AC: 9410 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1876 AN: 3472

East Asian (EAS) AF: 0.812 AC: 4176 AN: 5146

South Asian (SAS) AF: 0.766 AC: 3699 AN: 4826

European-Finnish (FIN) AF: 0.708 AC: 7502 AN: 10598

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38123 AN: 67936

Other (OTH) AF: 0.545 AC: 1154 AN: 2116

Alfa AF: 0.564 Hom.: 60961

Bravo AF: 0.551

Asia WGS AF: 0.753 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.34
PhyloP100		-1.3
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17689966; hg19: chr17-43910455; COSMIC: COSV53281880; COSMIC: COSV53281880;