17-45835124-C-G

Variant names:

• chr17-45835124-C-G
• rs878886
• ENST00000580955.6:n.1823C>G

Variant summary

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

The ENST00000580955.6(CRHR1):​n.1823C>G 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 0.158 in 262,402 control chromosomes in the GnomAD database, including 4,222 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 0.14 (2140 hom., cov: 34)
  • Exomes 𝑓: 0.18 (2082 hom.)
• Consequence: CRHR1 ENST00000580955.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 66 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.*360C>G		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.*360C>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.*360C>G		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21840 AN: 152142 Hom.: 2142 Cov.: 34

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.179 AC: 19668 AN: 110142 Hom.: 2082 Cov.: 0 AF XY: 0.179 AC XY: 9905 AN XY: 55282

African (AFR) AF: 0.0439 AC: 189 AN: 4302

American (AMR) AF: 0.155 AC: 714 AN: 4612

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 1051 AN: 4168

East Asian (EAS) AF: 0.000764 AC: 6 AN: 7852

South Asian (SAS) AF: 0.0924 AC: 381 AN: 4122

European-Finnish (FIN) AF: 0.0820 AC: 547 AN: 6674

Middle Eastern (MID) AF: 0.222 AC: 121 AN: 546

European-Non Finnish (NFE) AF: 0.217 AC: 15304 AN: 70454

Other (OTH) AF: 0.183 AC: 1355 AN: 7412

GnomAD4 genome AF: 0.143 AC: 21830 AN: 152260 Hom.: 2140 Cov.: 34 AF XY: 0.134 AC XY: 9997 AN XY: 74440

African (AFR) AF: 0.0429 AC: 1783 AN: 41576

American (AMR) AF: 0.176 AC: 2691 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0651 AC: 692 AN: 10622

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14760 AN: 67968

Other (OTH) AF: 0.182 AC: 385 AN: 2112

Alfa AF: 0.0808 Hom.: 110

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.5
DANN	Benign	0.36
PhyloP100		0.82
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: rs878886; hg19: chr17-43912490;