chr17-45835420-G-C

Position:

• chr17-45835420-G-C

Variant summary

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

The NM_004382.5(CRHR1):​c.*656G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 153,568 control chromosomes in the GnomAD database, including 2,166 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 (2142 hom., cov: 33)
  • Exomes 𝑓: 0.16 (24 hom.)
• Consequence: CRHR1 NM_004382.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548

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=-0.98).
• 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	Protein	UniProt
CRHR1	NM_004382.5	c.*656G>C		3_prime_UTR_variant	13/13	ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.*656G>C		3_prime_UTR_variant	15/15		NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.*656G>C		3_prime_UTR_variant	13/13	1	NM_004382.5	ENSP00000326060	P1
MAPT-AS1	ENST00000634876.2	n.604-6059C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21844 AN: 152164 Hom.: 2144 Cov.: 33

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: 0.0742

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.164 AC: 211 AN: 1286 Hom.: 24 Cov.: 0 AF XY: 0.175 AC XY: 156 AN XY: 892

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0278

Gnomad4 FIN exome AF: 0.0795

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.143 AC: 21834 AN: 152282 Hom.: 2142 Cov.: 33 AF XY: 0.134 AC XY: 10001 AN XY: 74474

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.183

Alfa AF: 0.0898 Hom.: 127

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	-0.98
CADD	Benign	12
DANN	Benign	0.27

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: rs4640231; hg19: chr17-43912786;