rs16940674

Positions:

• chr17-45833141-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004382.5(CRHR1):​c.774C>T​(p.Cys258Cys) variant causes a synonymous change. The variant allele was found at a frequency of 0.188 in 1,611,846 control chromosomes in the GnomAD database, including 32,679 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 (2135 hom., cov: 33)
  • Exomes 𝑓: 0.19 (30544 hom.)
• Consequence: CRHR1 NM_004382.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97

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]

CRHR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• 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.774C>T	p.Cys258Cys	synonymous_variant	9/13	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.774C>T	p.Cys258Cys	synonymous_variant	9/13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.249C>T	p.Cys83Cys	synonymous_variant	11/15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21803 AN: 152106 Hom.: 2137 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.145 AC: 36277 AN: 249506 Hom.: 3523 AF XY: 0.149 AC XY: 20118 AN XY: 135366

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.000667

Gnomad SAS exome AF: 0.0762

Gnomad FIN exome AF: 0.0677

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.193 AC: 281417 AN: 1459622 Hom.: 30544 Cov.: 36 AF XY: 0.190 AC XY: 138306 AN XY: 726240

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.000882

Gnomad4 SAS exome AF: 0.0796

Gnomad4 FIN exome AF: 0.0722

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.143 AC: 21793 AN: 152224 Hom.: 2135 Cov.: 33 AF XY: 0.134 AC XY: 9981 AN XY: 74440

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.182

Alfa AF: 0.192 Hom.: 2085

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	-0.31
CADD	Benign	14
DANN	Uncertain	0.98

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: rs16940674; hg19: chr17-43910507;