17-45816350-C-T

Variant names:

• chr17-45816350-C-T
• rs8072451
• NM_004382.5:c.122-113C>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.122-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,407,280 control chromosomes in the GnomAD database, including 29,871 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 0.15 (2223 hom., cov: 33)
  • Exomes 𝑓: 0.20 (27648 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 63 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=-0.94).
• 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.122-113C>T		intron_variant	Intron 2 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-113C>T		intron_variant	Intron 2 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-404-113C>T		intron_variant	Intron 4 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23165 AN: 152078 Hom.: 2225 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.199 AC: 249867 AN: 1255084 Hom.: 27648 AF XY: 0.196 AC XY: 121627 AN XY: 621308

African (AFR) AF: 0.0691 AC: 1955 AN: 28274

American (AMR) AF: 0.131 AC: 4231 AN: 32320

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 5342 AN: 21234

East Asian (EAS) AF: 0.000853 AC: 31 AN: 36338

South Asian (SAS) AF: 0.0806 AC: 5640 AN: 69932

European-Finnish (FIN) AF: 0.0753 AC: 3024 AN: 40148

Middle Eastern (MID) AF: 0.208 AC: 779 AN: 3754

European-Non Finnish (NFE) AF: 0.226 AC: 219255 AN: 970166

Other (OTH) AF: 0.182 AC: 9610 AN: 52918

GnomAD4 genome AF: 0.152 AC: 23164 AN: 152196 Hom.: 2223 Cov.: 33 AF XY: 0.142 AC XY: 10596 AN XY: 74412

African (AFR) AF: 0.0741 AC: 3076 AN: 41522

American (AMR) AF: 0.178 AC: 2725 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

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

European-Finnish (FIN) AF: 0.0649 AC: 689 AN: 10616

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

European-Non Finnish (NFE) AF: 0.217 AC: 14779 AN: 67984

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.197 Hom.: 5409

Bravo AF: 0.159

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.55
PhyloP100		-1.9
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: rs8072451; hg19: chr17-43893716;