rs3029044

chr17-45830275-C-CAGGTGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004382.5(CRHR1):c.555+61_555+62insAGGTGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,605,614 control chromosomes in the GnomAD database, including 32,546 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2112 hom., cov: 30)
  • Exomes 𝑓: 0.19 (30434 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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 -8 ACMG points.

• 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.555+61_555+62insAGGTGG		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.30+61_30+62insAGGTGG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.555+61_555+62insAGGTGG		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.604-915_604-914insCCACCT		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21778 AN: 152024 Hom.: 2114 Cov.: 30

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.193 AC: 281178 AN: 1453472 Hom.: 30434 Cov.: 32 AF XY: 0.191 AC XY: 137938 AN XY: 722494

Gnomad4 AFR exome AF: 0.0364

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.000866

Gnomad4 SAS exome AF: 0.0794

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.143 AC: 21768 AN: 152142 Hom.: 2112 Cov.: 30 AF XY: 0.134 AC XY: 9959 AN XY: 74400

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.183

Alfa AF: 0.165 Hom.: 294

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3029044; hg19: chr17-43907641;