17-45816520-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004382.5(CRHR1):c.179C>T(p.Ala60Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,614,102 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 73 hom. )

Consequence

CRHR1
NM_004382.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.37

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:

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

MAPT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012295485).

BP6

Variant 17-45816520-C-T is Benign according to our data. Variant chr17-45816520-C-T is described in ClinVar as [Benign]. Clinvar id is 771768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5 link	c.179C>T	p.Ala60Val	missense_variant	Exon 3 of 13	ENST00000314537.10	NP_004373.2	P34998-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10 link	c.179C>T	p.Ala60Val	missense_variant	Exon 3 of 13	1	NM_004382.5	ENSP00000326060.6		P34998-2
LINC02210-CRHR1	ENST00000634540 link	c.-347C>T		5_prime_UTR_variant	Exon 5 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

993

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00644

AC:

1603

AN:

248836

Hom.:

AF XY:

0.00625

AC XY:

845

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.00169

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00576

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00810

AC:

11841

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00805

AC XY:

5853

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00650

Gnomad4 NFE exome

AF:

0.00976

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.00652

AC:

993

AN:

152294

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00807

Hom.:

Bravo

AF:

0.00549

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00716

AC:

865

EpiCase

AF:

0.00851

EpiControl

AF:

0.00919

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.30

.;.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

D;D;D;D

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

.;L;L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.2

.;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.051

.;T;.;T

Sift4G

Uncertain

0.058

T;T;T;D

Polyphen

0.12, 0.24, 0.29

.;B;B;B

Vest4

0.15

MVP

0.57

MPC

0.64

ClinPred

0.012

GERP RS

4.1

Varity_R

0.55

gMVP

0.81

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

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