rs28364026

Variant names:

• chr17-45834928-G-A
• rs28364026
• ENST00000580955.6:n.1627G>A

Variant summary

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

The ENST00000580955.6(CRHR1):​n.1627G>A variant causes a non coding transcript exon 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 ENST00000580955.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 9 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 = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.*164G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.*164G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.*164G>A		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000488912.1

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

African (AFR) AF: 0.0112 AC: 215 AN: 19276

American (AMR) AF: 0.134 AC: 3281 AN: 24458

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 998 AN: 16404

East Asian (EAS) AF: 0.224 AC: 7282 AN: 32574

South Asian (SAS) AF: 0.108 AC: 5952 AN: 55322

European-Finnish (FIN) AF: 0.0415 AC: 1266 AN: 30538

Middle Eastern (MID) AF: 0.116 AC: 400 AN: 3460

European-Non Finnish (NFE) AF: 0.0436 AC: 24406 AN: 559272

Other (OTH) AF: 0.0702 AC: 2609 AN: 37140

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

African (AFR) AF: 0.0115 AC: 478 AN: 41578

American (AMR) AF: 0.112 AC: 1706 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 213 AN: 3466

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5168

South Asian (SAS) AF: 0.109 AC: 527 AN: 4828

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2862 AN: 68004

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

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
PhyloP100		0.32
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: rs28364026; hg19: chr17-43912294; COSMIC: COSV53278062; COSMIC: COSV53278062;