Variant rs16940665 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004382.5(CRHR1):c.669T>C(p.Thr223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,612,992 control chromosomes in the GnomAD database, including 32,770 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 ( 2139 hom., cov: 33)

Exomes 𝑓: 0.19 ( 30631 hom. )

Consequence

CRHR1
NM_004382.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.10

Variant links:

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]

CRHR1 links:

LINC02210-CRHR1 (HGNC:):

LINC02210-CRHR1 links:

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MAPT-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.802652).

BP7

Synonymous conserved (PhyloP=-5.1 with no splicing effect.

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	UniProt
CRHR1	NM_004382.5 linkuse as main transcript	c.669T>C	p.Thr223=	synonymous_variant	7/13	ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3 linkuse as main transcript	c.144T>C	p.Thr48=	synonymous_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10 linkuse as main transcript	c.669T>C	p.Thr223=	synonymous_variant	7/13	1	NM_004382.5	P1	P34998-2
MAPT-AS1	ENST00000634876.2 linkuse as main transcript	n.604-1169A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21838

AN:

152150

Hom.:

2141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0648

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.145

AC:

36154

AN:

248984

Hom.:

3513

AF XY:

0.149

AC XY:

20025

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000668

Gnomad SAS exome

AF:

0.0759

Gnomad FIN exome

AF:

0.0676

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.193

AC:

282562

AN:

1460724

Hom.:

30631

Cov.:

AF XY:

0.191

AC XY:

138799

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0795

Gnomad4 FIN exome

AF:

0.0720

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.143

AC:

21828

AN:

152268

Hom.:

2139

Cov.:

AF XY:

0.134

AC XY:

9994

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0430

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0739

Gnomad4 FIN

AF:

0.0648

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.213

Hom.:

4168

Bravo

AF:

0.148

TwinsUK

AF:

0.234

AC:

867

ALSPAC

AF:

0.241

AC:

930

ESP6500AA

AF:

0.0454

AC:

200

ESP6500EA

AF:

0.224

AC:

1925

ExAC

AF:

0.144

AC:

17510

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_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

Cadd

Benign

3.7

Dann

Benign

0.54

FATHMM_MKL

Benign

0.020

MutationTaster

Benign

9.8e-14

P;P;P;P;P;P

Vest4

0.70

GERP RS

-4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over