rs16940646

Variant names:

• chr17-45802545-A-C
• rs16940646
• NM_004382.5:c.34-4465A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.34-4465A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,212 control chromosomes in the GnomAD database, including 2,324 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 0.15 (2324 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004382.5. 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.34-4465A>C		intron	N/A	NP_004373.2
	CRHR1	NM_001145146.2		c.34-4465A>C		intron	N/A	NP_001138618.1
	CRHR1	NM_001145148.2		c.34-4465A>C		intron	N/A	NP_001138620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.34-4465A>C		intron	N/A	ENSP00000326060.6
	CRHR1	ENST00000398285.7	TSL:1	c.34-4465A>C		intron	N/A	ENSP00000381333.3
	CRHR1	ENST00000577353.5	TSL:1	c.34-4465A>C		intron	N/A	ENSP00000462016.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22020 AN: 152094 Hom.: 2311 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22076 AN: 152212 Hom.: 2324 Cov.: 33 AF XY: 0.142 AC XY: 10574 AN XY: 74424

African (AFR) AF: 0.297 AC: 12315 AN: 41504

American (AMR) AF: 0.0846 AC: 1293 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4824

European-Finnish (FIN) AF: 0.0902 AC: 957 AN: 10608

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6560 AN: 68016

Other (OTH) AF: 0.141 AC: 299 AN: 2116

Alfa AF: 0.115 Hom.: 474

Bravo AF: 0.151

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.75
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16940646; hg19: chr17-43879911;