Variant 6-31142614-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 0.28 ( 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

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=0.0013647377).

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/exons	MANE	UniProt
CCHCR1	NM_001105564.2 linkuse as main transcript	c.2594C>G	p.Ser865Cys	missense_variant	18/18	ENST00000396268.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCHCR1	ENST00000396268.8 linkuse as main transcript	c.2594C>G	p.Ser865Cys	missense_variant	18/18	1	NM_001105564.2	A2	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

GnomAD3 exomes

AF:

0.278

AC:

69694

AN:

250546

Hom.:

10434

AF XY:

0.280

AC XY:

37894

AN XY:

135422

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 SAS exome

AF:

0.235

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

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.283

AC:

43008

AN:

152198

Hom.:

6262

Cov.:

AF XY:

0.279

AC XY:

20792

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.0836

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.305

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

DANN

Benign

0.67

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.025

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

P;P;P;P;P

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over