rs1876830

Variant names:

• chr17-45833986-C-T
• rs1876830
• NM_004382.5:c.1066-21C>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.1066-21C>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 1,612,134 control chromosomes in the GnomAD database, including 32,769 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: 0.19 (30628 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 28 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=-0.82).
• 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.1066-21C>T		intron_variant	Intron 11 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.1066-21C>T		intron_variant	Intron 11 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.541-21C>T		intron_variant	Intron 13 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21827 AN: 152054 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: 0.0741

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.145 AC: 36250 AN: 249274 AF XY: 0.149

Gnomad AFR exome AF: 0.0396

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.000668

Gnomad FIN exome AF: 0.0673

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.193 AC: 281849 AN: 1459962 Hom.: 30628 Cov.: 39 AF XY: 0.191 AC XY: 138496 AN XY: 726364

African (AFR) AF: 0.0366 AC: 1224 AN: 33478

American (AMR) AF: 0.125 AC: 5601 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6697 AN: 26112

East Asian (EAS) AF: 0.000907 AC: 36 AN: 39700

South Asian (SAS) AF: 0.0795 AC: 6859 AN: 86234

European-Finnish (FIN) AF: 0.0721 AC: 3843 AN: 53272

Middle Eastern (MID) AF: 0.201 AC: 1160 AN: 5762

European-Non Finnish (NFE) AF: 0.221 AC: 245753 AN: 1110334

Other (OTH) AF: 0.177 AC: 10676 AN: 60350

GnomAD4 genome AF: 0.143 AC: 21817 AN: 152172 Hom.: 2141 Cov.: 32 AF XY: 0.134 AC XY: 9990 AN XY: 74408

African (AFR) AF: 0.0428 AC: 1777 AN: 41538

American (AMR) AF: 0.176 AC: 2688 AN: 15294

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

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

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

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10604

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

European-Non Finnish (NFE) AF: 0.217 AC: 14761 AN: 67946

Other (OTH) AF: 0.182 AC: 384 AN: 2110

Alfa AF: 0.195 Hom.: 1069

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	-0.82
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.018
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: rs1876830; hg19: chr17-43911352;