Genetic Variant CCHCR1:p.Ser253Arg (chr6-31154538-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105564.2(CCHCR1):c.759C>G(p.Ser253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,068 control chromosomes in the GnomAD database, including 150,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.41 ( 12542 hom., cov: 33)

Exomes 𝑓: 0.43 ( 138215 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037828386).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 link	c.759C>G	p.Ser253Arg	missense_variant	Exon 4 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.759C>G	p.Ser253Arg	missense_variant	Exon 4 of 18	1	NM_001105564.2	ENSP00000379566.3		Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61597

AN:

151974

Hom.:

12538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.383

GnomAD3 exomes

AF:

0.405

AC:

99566

AN:

245652

Hom.:

20506

AF XY:

0.404

AC XY:

54077

AN XY:

133972

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.432

AC:

631436

AN:

1459976

Hom.:

138215

Cov.:

AF XY:

0.430

AC XY:

312002

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.405

AC:

61617

AN:

152092

Hom.:

12542

Cov.:

AF XY:

0.402

AC XY:

29860

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.433

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.369

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.413

Hom.:

4387

Bravo

AF:

0.411

TwinsUK

AF:

0.460

AC:

1707

ALSPAC

AF:

0.456

AC:

1757

ESP6500AA

AF:

0.377

AC:

1140

ESP6500EA

AF:

0.429

AC:

2323

ExAC

AF:

0.404

AC:

47434

Asia WGS

AF:

0.392

AC:

1361

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0094

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

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.67

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

MetaRNN

Benign

0.0038

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

2.0

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

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.080

N;N;N;N;N;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.66

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

Sift4G

Benign

0.44

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

Polyphen

0.0040

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

Vest4

0.35

MutPred

0.16

.;Loss of phosphorylation at S164 (P = 0.0084);Loss of phosphorylation at S164 (P = 0.0084);.;.;.;Loss of phosphorylation at S164 (P = 0.0084);.;

MPC

0.50

ClinPred

0.0053

GERP RS

3.5

Varity_R

0.038

gMVP

0.45

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