chr17-45829462-G-A

Position:

• chr17-45829462-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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.434+141G>A		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-92+141G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.434+141G>A		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.604-101C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.0360

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.000893

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.175

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

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.181

Alfa AF: 0.186 Hom.: 797

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	-0.81
CADD	Benign	4.9
DANN	Benign	0.75

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: rs17689882; hg19: chr17-43906828;