17-45807036-C-T

Variant names:

• chr17-45807036-C-T
• rs12936511
• ENST00000634540.1:c.-466C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000634540.1(LINC02210-CRHR1):​c.-466C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 1,613,946 control chromosomes in the GnomAD database, including 1,257 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 0.030 (73 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1184 hom.)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28
• Publications: 14 publications found

Genes affected

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]

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]

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.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0297 (4526/152290) while in subpopulation NFE AF = 0.0437 (2970/68018). AF 95% confidence interval is 0.0424. There are 73 homozygotes in GnomAd4. There are 2143 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.60C>T	p.Pro20Pro	synonymous_variant	Exon 2 of 13	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02210-CRHR1	ENST00000634540.1	c.-466C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 4 of 15	2		ENSP00000488912.1
CRHR1	ENST00000314537.10	c.60C>T	p.Pro20Pro	synonymous_variant	Exon 2 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-466C>T		5_prime_UTR_variant	Exon 4 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4521 AN: 152172 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0311 AC: 7752 AN: 249060 AF XY: 0.0319

Gnomad AFR exome AF: 0.00852

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0456

Gnomad EAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0439

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0389 AC: 56908 AN: 1461656 Hom.: 1184 Cov.: 31 AF XY: 0.0384 AC XY: 27946 AN XY: 727132

African (AFR) AF: 0.00771 AC: 258 AN: 33480

American (AMR) AF: 0.0173 AC: 772 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 1196 AN: 26124

East Asian (EAS) AF: 0.0138 AC: 548 AN: 39700

South Asian (SAS) AF: 0.0131 AC: 1129 AN: 86230

European-Finnish (FIN) AF: 0.0404 AC: 2157 AN: 53342

Middle Eastern (MID) AF: 0.0291 AC: 168 AN: 5766

European-Non Finnish (NFE) AF: 0.0436 AC: 48520 AN: 1111908

Other (OTH) AF: 0.0358 AC: 2160 AN: 60388

GnomAD4 genome AF: 0.0297 AC: 4526 AN: 152290 Hom.: 73 Cov.: 33 AF XY: 0.0288 AC XY: 2143 AN XY: 74456

African (AFR) AF: 0.00989 AC: 411 AN: 41564

American (AMR) AF: 0.0259 AC: 396 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5178

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4826

European-Finnish (FIN) AF: 0.0404 AC: 429 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2970 AN: 68018

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0400 Hom.: 192

Bravo AF: 0.0281

Asia WGS AF: 0.0300 AC: 105 AN: 3476

EpiCase AF: 0.0419

EpiControl AF: 0.0425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.2
DANN	Benign	0.72
PhyloP100		-4.3
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 19

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

Other links and lift over

dbSNP: rs12936511; hg19: chr17-43884402;