Genetic Variant CCHCR1:p.Gly687Arg (chr6-31144891-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001105564.2(CCHCR1):c.2059G>C(p.Gly687Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.18

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1518004).

BP6

Variant 6-31144891-C-G is Benign according to our data. Variant chr6-31144891-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2513471.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105564.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCHCR1	NM_001105564.2	MANE Select	c.2059G>C	p.Gly687Arg	missense	Exon 14 of 18	NP_001099034.1	Q8TD31-2
CCHCR1	NM_001394641.1		c.2086G>C	p.Gly696Arg	missense	Exon 14 of 18	NP_001381570.1
CCHCR1	NM_001105563.3		c.1951G>C	p.Gly651Arg	missense	Exon 14 of 18	NP_001099033.1	Q8TD31-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.2059G>C	p.Gly687Arg	missense	Exon 14 of 18	ENSP00000379566.3	Q8TD31-2
CCHCR1	ENST00000451521.6	TSL:1	c.1951G>C	p.Gly651Arg	missense	Exon 14 of 18	ENSP00000401039.2	Q8TD31-3
CCHCR1	ENST00000376266.9	TSL:1	c.1792G>C	p.Gly598Arg	missense	Exon 14 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250956

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726954

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000671

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111848

Other (OTH)

AF:

0.0000166

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.76

M_CAP

Benign

0.0072

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.2

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.56

REVEL

Benign

0.090

Sift

Benign

0.094

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.20

MutPred

0.48

Gain of MoRF binding (P = 0.0214)

MVP

0.24

MPC

0.61

ClinPred

0.11

GERP RS

2.3

Varity_R

0.069

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over