17-45829462-G-A

Variant names:

• chr17-45829462-G-A
• rs17689882
• NM_004382.5:c.434+141G>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.434+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,354,770 control chromosomes in the GnomAD database, including 26,758 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 (2129 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24629 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 77 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=-0.81).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	NM_004382.5	MANE Select	c.434+141G>A		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.435-99G>A		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.434+141G>A		intron	N/A	NP_001138620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.434+141G>A		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.435-99G>A		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.434+141G>A		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21795 AN: 152092 Hom.: 2131 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: 0.0743

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.190 AC: 227934 AN: 1202560 Hom.: 24629 Cov.: 16 AF XY: 0.187 AC XY: 112072 AN XY: 598532

African (AFR) AF: 0.0360 AC: 986 AN: 27386

American (AMR) AF: 0.131 AC: 4202 AN: 32026

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 5663 AN: 22386

East Asian (EAS) AF: 0.000893 AC: 31 AN: 34722

South Asian (SAS) AF: 0.0795 AC: 5708 AN: 71790

European-Finnish (FIN) AF: 0.0714 AC: 3413 AN: 47818

Middle Eastern (MID) AF: 0.200 AC: 1047 AN: 5230

European-Non Finnish (NFE) AF: 0.217 AC: 197924 AN: 910032

Other (OTH) AF: 0.175 AC: 8960 AN: 51170

GnomAD4 genome AF: 0.143 AC: 21785 AN: 152210 Hom.: 2129 Cov.: 32 AF XY: 0.134 AC XY: 9982 AN XY: 74436

African (AFR) AF: 0.0429 AC: 1781 AN: 41536

American (AMR) AF: 0.175 AC: 2679 AN: 15278

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

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0744 AC: 359 AN: 4828

European-Finnish (FIN) AF: 0.0648 AC: 689 AN: 10626

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

European-Non Finnish (NFE) AF: 0.217 AC: 14734 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.200 Hom.: 5212

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	-0.81
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		0.032
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: rs17689882; hg19: chr17-43906828;