rs171442

chr17-45814540-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt
CRHR1	NM_004382.5	c.122-1923A>G		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-404-1923A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-1923A>G		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.2593+11043T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.903

Alfa AF: 0.899 Hom.: 13654

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

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: rs171442; hg19: chr17-43891906;