dbSNP rs130068: CCHCR1:p.Arg506Trp (chr6-31148469-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105564.2(CCHCR1):c.1516C>T(p.Arg506Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,611,098 control chromosomes in the GnomAD database, including 160,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 14675 hom., cov: 32)

Exomes 𝑓: 0.44 ( 145512 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.209

Publications

32 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5869737E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 link	c.1516C>T	p.Arg506Trp	missense_variant	Exon 10 of 18	ENST00000396268.8	NP_001099034.1	Q8TD31-2Q769H0Q2TB68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8 link	c.1516C>T	p.Arg506Trp	missense_variant	Exon 10 of 18	1	NM_001105564.2	ENSP00000379566.3		Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66673

AN:

151924

Hom.:

14676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.467

GnomAD2 exomes

AF:

0.440

AC:

108347

AN:

246312

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.448

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.443

AC:

647025

AN:

1459056

Hom.:

145512

Cov.:

AF XY:

0.445

AC XY:

323115

AN XY:

725864

show subpopulations

African (AFR)

AF:

0.419

AC:

14031

AN:

33452

American (AMR)

AF:

0.413

AC:

18472

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

13915

AN:

26120

East Asian (EAS)

AF:

0.289

AC:

11481

AN:

39694

South Asian (SAS)

AF:

0.458

AC:

39447

AN:

86182

European-Finnish (FIN)

AF:

0.514

AC:

26877

AN:

52308

Middle Eastern (MID)

AF:

0.543

AC:

3128

AN:

5762

European-Non Finnish (NFE)

AF:

0.443

AC:

491865

AN:

1110508

Other (OTH)

AF:

0.461

AC:

27809

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16999

33998

50996

67995

84994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.439

AC:

66695

AN:

152042

Hom.:

14675

Cov.:

AF XY:

0.440

AC XY:

32713

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.422

AC:

17479

AN:

41462

American (AMR)

AF:

0.408

AC:

6224

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1777

AN:

3472

East Asian (EAS)

AF:

0.291

AC:

1501

AN:

5150

South Asian (SAS)

AF:

0.420

AC:

2022

AN:

4820

European-Finnish (FIN)

AF:

0.527

AC:

5582

AN:

10588

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30421

AN:

67964

Other (OTH)

AF:

0.464

AC:

981

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1988

3975

5963

7950

9938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.448

Hom.:

33848

Bravo

AF:

0.434

TwinsUK

AF:

0.436

AC:

1617

ALSPAC

AF:

0.434

AC:

1674

ESP6500AA

AF:

0.434

AC:

1312

ESP6500EA

AF:

0.444

AC:

2408

ExAC

AF:

0.437

AC:

51479

Asia WGS

AF:

0.421

AC:

1468

AN:

3478

EpiCase

AF:

0.473

EpiControl

AF:

0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0065

.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.78

.;.;.;T

MetaRNN

Benign

0.00016

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

.;L;.;.

PhyloP100

0.21

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.0030

B;B;.;.

Vest4

0.15

MPC

0.46

ClinPred

0.0053

GERP RS

1.1

Varity_R

0.12

gMVP

0.19

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs130068

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over