17-45823708-A-G

Variant names:

• chr17-45823708-A-G
• rs173365
• NM_004382.5:c.327+2268A>G

Variant summary

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

The NM_004382.5(CRHR1):​c.327+2268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,072 control chromosomes in the GnomAD database, including 24,764 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 (24764 hom., cov: 32)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.327+2268A>G		intron_variant	Intron 4 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.327+2268A>G		intron_variant	Intron 4 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-199+2268A>G		intron_variant	Intron 6 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84966 AN: 151954 Hom.: 24758 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.559 AC: 84992 AN: 152072 Hom.: 24764 Cov.: 32 AF XY: 0.572 AC XY: 42479 AN XY: 74326

African (AFR) AF: 0.432 AC: 17917 AN: 41492

American (AMR) AF: 0.615 AC: 9401 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4705 AN: 5148

South Asian (SAS) AF: 0.779 AC: 3759 AN: 4824

European-Finnish (FIN) AF: 0.705 AC: 7446 AN: 10566

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38071 AN: 67962

Other (OTH) AF: 0.540 AC: 1141 AN: 2112

Alfa AF: 0.574 Hom.: 16973

Bravo AF: 0.546

Asia WGS AF: 0.789 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs173365; hg19: chr17-43901074;