17-45830600-G-A

Variant names:

• chr17-45830600-G-A
• rs16940668
• NM_004382.5:c.709+30G>A

Variant summary

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

The NM_004382.5(CRHR1):​c.709+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,577,396 control chromosomes in the GnomAD database, including 32,168 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 (2139 hom., cov: 33)
  • Exomes 𝑓: 0.19 (30029 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 24 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 (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.709+30G>A		intron_variant	Intron 7 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.709+30G>A		intron_variant	Intron 7 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.184+30G>A		intron_variant	Intron 9 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21825 AN: 152122 Hom.: 2141 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.148 AC: 32587 AN: 220474 AF XY: 0.151

Gnomad AFR exome AF: 0.0408

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.000691

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.194 AC: 276940 AN: 1425156 Hom.: 30029 Cov.: 34 AF XY: 0.192 AC XY: 135233 AN XY: 704592

African (AFR) AF: 0.0369 AC: 1215 AN: 32940

American (AMR) AF: 0.125 AC: 5330 AN: 42534

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6246 AN: 24352

East Asian (EAS) AF: 0.000891 AC: 35 AN: 39288

South Asian (SAS) AF: 0.0797 AC: 6490 AN: 81384

European-Finnish (FIN) AF: 0.0748 AC: 3530 AN: 47208

Middle Eastern (MID) AF: 0.202 AC: 1097 AN: 5438

European-Non Finnish (NFE) AF: 0.222 AC: 242550 AN: 1093094

Other (OTH) AF: 0.177 AC: 10447 AN: 58918

GnomAD4 genome AF: 0.143 AC: 21815 AN: 152240 Hom.: 2139 Cov.: 33 AF XY: 0.134 AC XY: 9987 AN XY: 74434

African (AFR) AF: 0.0430 AC: 1786 AN: 41566

American (AMR) AF: 0.176 AC: 2690 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0738 AC: 356 AN: 4826

European-Finnish (FIN) AF: 0.0646 AC: 686 AN: 10624

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

European-Non Finnish (NFE) AF: 0.217 AC: 14754 AN: 67954

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.179 Hom.: 529

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	-0.90
CADD	Benign	2.1
DANN	Benign	0.87
PhyloP100		-0.48
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

Other links and lift over

dbSNP: rs16940668; hg19: chr17-43907966;