17-45830379-C-T

Variant names:

• chr17-45830379-C-T
• rs1876831
• NM_004382.5:c.556-38C>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.556-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,587,388 control chromosomes in the GnomAD database, including 32,128 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: 32)
  • Exomes 𝑓: 0.19 (29988 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 79 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.556-38C>T		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.643-38C>T		intron	N/A	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.556-38C>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.556-38C>T		intron	N/A	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.643-38C>T		intron	N/A	ENSP00000381333.3	P34998-1
	CRHR1	ENST00000577353.5	TSL:1	c.556-38C>T		intron	N/A	ENSP00000462016.1	P34998-4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21827 AN: 152042 Hom.: 2142 Cov.: 32

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: 0.0649

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.141 AC: 32307 AN: 228874 AF XY: 0.144

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.000671

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.193 AC: 277279 AN: 1435228 Hom.: 29988 Cov.: 34 AF XY: 0.191 AC XY: 135482 AN XY: 710474

African (AFR) AF: 0.0366 AC: 1219 AN: 33262

American (AMR) AF: 0.124 AC: 5406 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6117 AN: 24176

East Asian (EAS) AF: 0.000887 AC: 35 AN: 39454

South Asian (SAS) AF: 0.0785 AC: 6446 AN: 82078

European-Finnish (FIN) AF: 0.0716 AC: 3688 AN: 51482

Middle Eastern (MID) AF: 0.199 AC: 1120 AN: 5622

European-Non Finnish (NFE) AF: 0.221 AC: 242785 AN: 1096390

Other (OTH) AF: 0.176 AC: 10463 AN: 59294

GnomAD4 genome AF: 0.143 AC: 21817 AN: 152160 Hom.: 2140 Cov.: 32 AF XY: 0.134 AC XY: 9989 AN XY: 74406

African (AFR) AF: 0.0429 AC: 1784 AN: 41558

American (AMR) AF: 0.176 AC: 2687 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5166

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

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10606

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14754 AN: 67932

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.178 Hom.: 521

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	2.5
DANN	Benign	0.71
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1876831; hg19: chr17-43907745;