Genetic Variant NM_001105564.2:c.2594C>G (chr6-31142614-G-C) – 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.2594C>G(p.Ser865Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,611,658 control chromosomes in the GnomAD database, including 77,250 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 0.28 ( 6262 hom., cov: 33)

Exomes 𝑓: 0.31 ( 70988 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.473

Publications

62 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0013647377).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 link	c.2594C>G	p.Ser865Cys	missense_variant	Exon 18 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.2594C>G	p.Ser865Cys	missense_variant	Exon 18 of 18	1	NM_001105564.2	ENSP00000379566.3		Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42989

AN:

152080

Hom.:

6262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.0834

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.308

GnomAD2 exomes

AF:

0.278

AC:

69694

AN:

250546

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.306

AC:

446964

AN:

1459460

Hom.:

70988

Cov.:

AF XY:

0.305

AC XY:

221086

AN XY:

725938

show subpopulations

African (AFR)

AF:

0.233

AC:

7774

AN:

33436

American (AMR)

AF:

0.277

AC:

12367

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

11482

AN:

26116

East Asian (EAS)

AF:

0.0681

AC:

2702

AN:

39688

South Asian (SAS)

AF:

0.237

AC:

20417

AN:

86206

European-Finnish (FIN)

AF:

0.299

AC:

15725

AN:

52622

Middle Eastern (MID)

AF:

0.333

AC:

1894

AN:

5680

European-Non Finnish (NFE)

AF:

0.320

AC:

355675

AN:

1110706

Other (OTH)

AF:

0.314

AC:

18928

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

15305

30609

45914

61218

76523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11534

23068

34602

46136

57670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.283

AC:

43008

AN:

152198

Hom.:

6262

Cov.:

AF XY:

0.279

AC XY:

20792

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.236

AC:

9800

AN:

41534

American (AMR)

AF:

0.265

AC:

4062

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1446

AN:

3472

East Asian (EAS)

AF:

0.0836

AC:

433

AN:

5182

South Asian (SAS)

AF:

0.219

AC:

1060

AN:

4830

European-Finnish (FIN)

AF:

0.317

AC:

3355

AN:

10586

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21613

AN:

67972

Other (OTH)

AF:

0.305

AC:

645

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1600

3201

4801

6402

8002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.317

Hom.:

1799

Bravo

AF:

0.281

TwinsUK

AF:

0.318

AC:

1180

ALSPAC

AF:

0.325

AC:

1254

ESP6500AA

AF:

0.248

AC:

1094

ESP6500EA

AF:

0.323

AC:

2776

ExAC

AF:

0.275

AC:

33442

Asia WGS

AF:

0.158

AC:

551

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.3

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0049

.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.59

.;.;.;T

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.28

.;N;.;.

PhyloP100

-0.47

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.093

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.079

MPC

0.41

ClinPred

0.0038

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.15

Mutation Taster

=100/0

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

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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