Genetic Variant CCHCR1:c.-52+167G>T (chr6-31158000-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000376266.9(CCHCR1):c.-52+167G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 254,130 control chromosomes in the GnomAD database, including 10,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6607 hom., cov: 28)

Exomes 𝑓: 0.27 ( 4182 hom. )

Consequence

CCHCR1
ENST00000376266.9 intron

Scores

Splicing: ADA: 0.00007773

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.865

Publications

34 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 (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 link	c.-400G>T		upstream_gene_variant		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.-400G>T		upstream_gene_variant		1	NM_001105564.2	ENSP00000379566.3		Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43963

AN:

151482

Hom.:

6606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.0795

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.265

AC:

27200

AN:

102532

Hom.:

4182

Cov.:

AF XY:

0.265

AC XY:

14611

AN XY:

55078

show subpopulations

African (AFR)

AF:

0.298

AC:

964

AN:

3232

American (AMR)

AF:

0.238

AC:

1157

AN:

4852

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

925

AN:

2822

East Asian (EAS)

AF:

0.0613

AC:

358

AN:

5840

South Asian (SAS)

AF:

0.261

AC:

4144

AN:

15868

European-Finnish (FIN)

AF:

0.245

AC:

937

AN:

3824

Middle Eastern (MID)

AF:

0.247

AC:

AN:

392

European-Non Finnish (NFE)

AF:

0.284

AC:

17112

AN:

60350

Other (OTH)

AF:

0.281

AC:

1506

AN:

5352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

928

1855

2783

3710

4638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.290

AC:

43973

AN:

151598

Hom.:

6607

Cov.:

AF XY:

0.282

AC XY:

20890

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.320

AC:

13178

AN:

41232

American (AMR)

AF:

0.243

AC:

3711

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1127

AN:

3468

East Asian (EAS)

AF:

0.0799

AC:

413

AN:

5172

South Asian (SAS)

AF:

0.251

AC:

1203

AN:

4790

European-Finnish (FIN)

AF:

0.228

AC:

2404

AN:

10530

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.308

AC:

20905

AN:

67852

Other (OTH)

AF:

0.276

AC:

580

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1509

3017

4526

6034

7543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.302

Hom.:

29347

Bravo

AF:

0.295

Asia WGS

AF:

0.195

AC:

677

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.9

(source)

DANN

Benign

0.59

PhyloP100

0.86

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.0040

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