Variant rs130076 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001105564.2(CCHCR1):c.592C>T(p.Arg198Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,609,422 control chromosomes in the GnomAD database, including 37,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2434 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35034 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

CCHCR1 (HGNC:13930): (coiled-coil alpha-helical rod protein 1) This gene encodes a protein with five coiled-coil alpha-helical rod domains that is thought to act as a regulator of mRNA metabolism through its interaction with mRNA-decapping protein 4. It localizes to P-bodies, the site of mRNA metabolism, with an N-terminus that is required for this subcellular localization, suggesting it is a P-body component. Naturally occurring mutations in this gene are associated with psoriasis. [provided by RefSeq, May 2017]

CCHCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011596978).

BP6

Variant 6-31154705-G-A is Benign according to our data. Variant chr6-31154705-G-A is described in ClinVar as [Benign]. Clinvar id is 1283507.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 linkuse as main transcript	c.592C>T	p.Arg198Trp	missense_variant	4/18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8 linkuse as main transcript	c.592C>T	p.Arg198Trp	missense_variant	4/18	1	NM_001105564.2	ENSP00000379566	A2	Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25992

AN:

152100

Hom.:

2430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.156

AC:

37608

AN:

241488

Hom.:

3542

AF XY:

0.160

AC XY:

21115

AN XY:

132160

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.210

AC:

306354

AN:

1457204

Hom.:

35034

Cov.:

AF XY:

0.208

AC XY:

150869

AN XY:

725186

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.0793

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.0220

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.171

AC:

26001

AN:

152218

Hom.:

2434

Cov.:

AF XY:

0.165

AC XY:

12284

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.0403

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.203

Hom.:

3410

Bravo

AF:

0.168

TwinsUK

AF:

0.240

AC:

891

ALSPAC

AF:

0.241

AC:

930

ESP6500AA

AF:

0.157

AC:

474

ESP6500EA

AF:

0.210

AC:

1138

ExAC

AF:

0.157

AC:

18338

Asia WGS

AF:

0.0750

AC:

264

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.208

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

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 22182809) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

.;T;T;.;T;T;T;.;T;T;T;.;T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.86

.;.;.;D;D;D;.;D;D;D;.;D;.;.;T

MetaRNN

Benign

0.0012

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;M;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.064

Sift

Benign

0.064

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.053

T;T;T;D;.;.;.;.;.;T;.;.;.;.;.

Polyphen

0.017

B;B;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.20

MPC

0.51

ClinPred

0.035

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.25

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