Variant 17-45830440-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004382.5(CRHR1):c.579C>T(p.Ala193Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,612,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

CRHR1
NM_004382.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.75

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: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]

LINC02210-CRHR1 links:

CRHR1 (HGNC:):

CRHR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054934323).

BP6

Variant 17-45830440-C-T is Benign according to our data. Variant chr17-45830440-C-T is described in ClinVar as [Benign]. Clinvar id is 708229.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.76 with no splicing effect.

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5 linkuse as main transcript	c.579C>T	p.Ala193Ala	synonymous_variant	7/13	ENST00000314537.10	NP_004373.2	P34998-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10 linkuse as main transcript	c.579C>T	p.Ala193Ala	synonymous_variant	7/13	1	NM_004382.5	ENSP00000326060.6		P34998-2
LINC02210-CRHR1	ENST00000634540.1 linkuse as main transcript	c.54C>T	p.Ala18Ala	synonymous_variant	9/15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000777

AC:

193

AN:

248350

Hom.:

AF XY:

0.000788

AC XY:

106

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00562

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.00372

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1459980

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

184

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00275

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00369

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000506

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00541

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000610

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

5.8

DANN

Benign

0.80

DEOGEN2

Benign

0.065

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0055

MutationTaster

Benign

1.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

Vest4

0.22

MVP

0.72

GERP RS

-11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over