rs28364026

chr17-45834928-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):c.*164G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 930,714 control chromosomes in the GnomAD database, including 2,514 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 0.050 (348 hom., cov: 33)
  • Exomes 𝑓: 0.060 (2166 hom.)
• Consequence: CRHR1 NM_004382.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.*164G>A		3_prime_UTR_variant	13/13	ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.*164G>A		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.*164G>A		3_prime_UTR_variant	13/13	1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.604-5567C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7575 AN: 152152 Hom.: 343 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0615

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0794

GnomAD4 exome AF: 0.0596 AC: 46409 AN: 778444 Hom.: 2166 Cov.: 10 AF XY: 0.0612 AC XY: 24012 AN XY: 392578

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0415

Gnomad4 NFE exome AF: 0.0436

Gnomad4 OTH exome AF: 0.0702

GnomAD4 genome AF: 0.0498 AC: 7587 AN: 152270 Hom.: 348 Cov.: 33 AF XY: 0.0534 AC XY: 3974 AN XY: 74446

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0615

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0857

Alfa AF: 0.0416 Hom.: 30

Bravo AF: 0.0550

Asia WGS AF: 0.180 AC: 627 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	6.1
Dann	Benign	0.30

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: rs28364026; hg19: chr17-43912294; COSMIC: COSV53278062; COSMIC: COSV53278062;