ENST00000580955.6:n.629_630insAGGTGG

Variant names:

• chr17-45830275-C-CAGGTGG
• rs3029044
• ENST00000580955.6:n.629_630insAGGTGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000580955.6(CRHR1):​n.629_630insAGGTGG variant causes a non coding transcript exon 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 ENST00000580955.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000580955.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	NM_004382.5	MANE Select	c.555+61_555+62insAGGTGG		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.642+61_642+62insAGGTGG		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.555+61_555+62insAGGTGG		intron	N/A	NP_001138620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000580955.6	TSL:1	n.629_630insAGGTGG		non_coding_transcript_exon	Exon 6 of 12
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.555+61_555+62insAGGTGG		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.642+61_642+62insAGGTGG		intron	N/A	ENSP00000381333.3

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

African (AFR) AF: 0.0364 AC: 1210 AN: 33264

American (AMR) AF: 0.125 AC: 5461 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6621 AN: 25784

East Asian (EAS) AF: 0.000866 AC: 34 AN: 39266

South Asian (SAS) AF: 0.0794 AC: 6782 AN: 85384

European-Finnish (FIN) AF: 0.0719 AC: 3765 AN: 52350

Middle Eastern (MID) AF: 0.202 AC: 1155 AN: 5732

European-Non Finnish (NFE) AF: 0.222 AC: 245522 AN: 1107852

Other (OTH) AF: 0.177 AC: 10628 AN: 60056

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

African (AFR) AF: 0.0429 AC: 1783 AN: 41550

American (AMR) AF: 0.175 AC: 2684 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3468

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

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

European-Finnish (FIN) AF: 0.0648 AC: 688 AN: 10612

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

European-Non Finnish (NFE) AF: 0.217 AC: 14719 AN: 67908

Other (OTH) AF: 0.183 AC: 387 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=34/66	disease causing

Splicing

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

Other links and lift over

dbSNP: rs3029044; hg19: chr17-43907641;