17-45827031-C-T

Position:

• chr17-45827031-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.328-2184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,240 control chromosomes in the GnomAD database, including 2,134 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 (2133 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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:):

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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/exons	MANE	UniProt
CRHR1	NM_004382.5	c.328-2184C>T		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-198-2184C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.328-2184C>T		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.1145G>A		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21807 AN: 152022 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.110 AC: 11 AN: 100 Hom.: 1 Cov.: 0 AF XY: 0.155 AC XY: 9 AN XY: 58

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.143 AC: 21797 AN: 152140 Hom.: 2133 Cov.: 32 AF XY: 0.134 AC XY: 9983 AN XY: 74392

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.183

Alfa AF: 0.190 Hom.: 1269

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	-0.95
CADD	Benign	5.5
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs17689824; hg19: chr17-43904397;