chr17-45814540-A-G

Variant names:

• chr17-45814540-A-G
• rs171442
• NM_004382.5:c.122-1923A>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.122-1923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,264 control chromosomes in the GnomAD database, including 61,321 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 0.89 (61321 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.122-1923A>G		intron_variant	Intron 2 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-1923A>G		intron_variant	Intron 2 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-404-1923A>G		intron_variant	Intron 4 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136099 AN: 152146 Hom.: 61295 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.894 AC: 136176 AN: 152264 Hom.: 61321 Cov.: 33 AF XY: 0.898 AC XY: 66852 AN XY: 74448

African (AFR) AF: 0.780 AC: 32390 AN: 41520

American (AMR) AF: 0.940 AC: 14379 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 0.975 AC: 4705 AN: 4826

European-Finnish (FIN) AF: 0.952 AC: 10113 AN: 10622

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63208 AN: 68024

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.897 Hom.: 13896

Bravo AF: 0.888

Asia WGS AF: 0.972 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		-0.12
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: rs171442; hg19: chr17-43891906;