17-45798051-A-T

Variant names:

• chr17-45798051-A-T
• rs34174655
• NM_004382.5:c.34-8959A>T

Variant summary

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

The NM_001145146.2(CRHR1):​c.34-8959A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,124 control chromosomes in the GnomAD database, including 631 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 0.087 (631 hom., cov: 31)
• Consequence: CRHR1 NM_001145146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145146.2. 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.34-8959A>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.34-8959A>T		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.34-8959A>T		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.34-8959A>T		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.34-8959A>T		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.34-8959A>T		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13276 AN: 152006 Hom.: 629 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0825

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

GnomAD4 genome AF: 0.0874 AC: 13296 AN: 152124 Hom.: 631 Cov.: 31 AF XY: 0.0856 AC XY: 6372 AN XY: 74396

African (AFR) AF: 0.107 AC: 4430 AN: 41484

American (AMR) AF: 0.0553 AC: 845 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5162

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4818

European-Finnish (FIN) AF: 0.0905 AC: 959 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0934 AC: 6349 AN: 67990

Other (OTH) AF: 0.0816 AC: 172 AN: 2108

Alfa AF: 0.0873 Hom.: 84

Bravo AF: 0.0854

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.85
PhyloP100		-0.15
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: rs34174655; hg19: chr17-43875417;