17-45834159-C-T

Variant names:

• chr17-45834159-C-T
• rs1876828
• NM_004382.5:c.1107+111C>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.1107+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,336,388 control chromosomes in the GnomAD database, including 21,739 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 (2141 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19598 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 97 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004382.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	NM_004382.5	MANE Select	c.1107+111C>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.1194+111C>T		intron	N/A	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.1065+310C>T		intron	N/A	NP_001138620.1	P34998-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.1107+111C>T		intron	N/A	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.1194+111C>T		intron	N/A	ENSP00000381333.3	P34998-1
	CRHR1	ENST00000577353.5	TSL:1	c.1065+310C>T		intron	N/A	ENSP00000462016.1	P34998-4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21838 AN: 152154 Hom.: 2143 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.171 AC: 202273 AN: 1184116 Hom.: 19598 AF XY: 0.170 AC XY: 101827 AN XY: 599240

African (AFR) AF: 0.0356 AC: 1024 AN: 28734

American (AMR) AF: 0.122 AC: 5231 AN: 42776

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 5683 AN: 23072

East Asian (EAS) AF: 0.000752 AC: 29 AN: 38582

South Asian (SAS) AF: 0.0772 AC: 6080 AN: 78794

European-Finnish (FIN) AF: 0.0703 AC: 3309 AN: 47098

Middle Eastern (MID) AF: 0.192 AC: 983 AN: 5110

European-Non Finnish (NFE) AF: 0.198 AC: 171655 AN: 868748

Other (OTH) AF: 0.162 AC: 8279 AN: 51202

GnomAD4 genome AF: 0.143 AC: 21828 AN: 152272 Hom.: 2141 Cov.: 32 AF XY: 0.134 AC XY: 9991 AN XY: 74450

African (AFR) AF: 0.0428 AC: 1781 AN: 41568

American (AMR) AF: 0.176 AC: 2696 AN: 15314

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

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0737 AC: 356 AN: 4830

European-Finnish (FIN) AF: 0.0649 AC: 690 AN: 10628

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

European-Non Finnish (NFE) AF: 0.217 AC: 14757 AN: 67960

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.163 Hom.: 770

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.3
DANN	Benign	0.36
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1876828;

hg19: chr17-43911525;