Genetic Variant NM_001105564.2:c.1581-118T>C (chr6-31145926-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001105564.2(CCHCR1):c.1581-118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 635,876 control chromosomes in the GnomAD database, including 89 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 0.010 ( 11 hom., cov: 32)

Exomes 𝑓: 0.013 ( 78 hom. )

Consequence

CCHCR1
NM_001105564.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

2 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=-0.84).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0101 (1537/152354) while in subpopulation SAS AF = 0.0194 (94/4834). AF 95% confidence interval is 0.0163. There are 11 homozygotes in GnomAd4. There are 788 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2 link	c.1581-118T>C		intron_variant	Intron 10 of 17	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.1581-118T>C		intron_variant	Intron 10 of 17	1	NM_001105564.2	ENSP00000379566.3		Q8TD31-2

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1538

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.0247

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0133

AC:

6414

AN:

483522

Hom.:

AF XY:

0.0140

AC XY:

3563

AN XY:

254850

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

13194

American (AMR)

AF:

0.00970

AC:

198

AN:

20416

Ashkenazi Jewish (ASJ)

AF:

0.00241

AC:

AN:

14500

East Asian (EAS)

AF:

0.000444

AC:

AN:

31530

South Asian (SAS)

AF:

0.0243

AC:

1193

AN:

49170

European-Finnish (FIN)

AF:

0.0202

AC:

753

AN:

37210

Middle Eastern (MID)

AF:

0.0462

AC:

171

AN:

3698

European-Non Finnish (NFE)

AF:

0.0130

AC:

3717

AN:

286548

Other (OTH)

AF:

0.0114

AC:

311

AN:

27256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

332

664

996

1328

1660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.0101

AC:

1537

AN:

152354

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

788

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41584

American (AMR)

AF:

0.00725

AC:

111

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0194

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0247

AC:

262

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0139

AC:

945

AN:

68032

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0120

Hom.:

Bravo

AF:

0.00827

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.1

(source)

DANN

Benign

0.66

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(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