chr17-45835216-C-T

Variant names:

• chr17-45835216-C-T
• rs878887
• ENST00000580955.6:n.1915C>T

Variant summary

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

The NM_004382.5(CRHR1):​c.*452C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 169,452 control chromosomes in the GnomAD database, including 2,482 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 (2143 hom., cov: 33)
  • Exomes 𝑓: 0.18 (339 hom.)
• Consequence: CRHR1 NM_004382.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 41 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=-0.89).
• 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.*452C>T		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.*452C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.*452C>T		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21856 AN: 152150 Hom.: 2145 Cov.: 33

Gnomad AFR AF: 0.0432

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: 0.0650

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.181 AC: 3113 AN: 17184 Hom.: 339 Cov.: 0 AF XY: 0.181 AC XY: 1567 AN XY: 8664

African (AFR) AF: 0.0417 AC: 27 AN: 648

American (AMR) AF: 0.156 AC: 210 AN: 1342

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 136 AN: 546

East Asian (EAS) AF: 0.00 AC: 0 AN: 762

South Asian (SAS) AF: 0.0998 AC: 85 AN: 852

European-Finnish (FIN) AF: 0.0798 AC: 67 AN: 840

Middle Eastern (MID) AF: 0.229 AC: 16 AN: 70

European-Non Finnish (NFE) AF: 0.215 AC: 2386 AN: 11100

Other (OTH) AF: 0.182 AC: 186 AN: 1024

GnomAD4 genome AF: 0.143 AC: 21846 AN: 152268 Hom.: 2143 Cov.: 33 AF XY: 0.134 AC XY: 10010 AN XY: 74466

African (AFR) AF: 0.0431 AC: 1789 AN: 41548

American (AMR) AF: 0.176 AC: 2690 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4830

European-Finnish (FIN) AF: 0.0650 AC: 691 AN: 10626

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

European-Non Finnish (NFE) AF: 0.217 AC: 14770 AN: 67990

Other (OTH) AF: 0.183 AC: 387 AN: 2116

Alfa AF: 0.197 Hom.: 2253

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	-0.89
CADD	Benign	1.5
DANN	Benign	0.84
PhyloP100		-2.1
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: rs878887; hg19: chr17-43912582;