Genetic Variant CCDC158:c.2882+122G>A (chr4-76332310-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394954.1(CCDC158):c.2882+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 708,360 control chromosomes in the GnomAD database, including 79 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 0.014 ( 16 hom., cov: 32)

Exomes 𝑓: 0.014 ( 63 hom. )

Consequence

CCDC158
NM_001394954.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

0 publications found

Variant links:

Genes affected

CCDC158 (HGNC:26374): (coiled-coil domain containing 158)

CCDC158 Gene-Disease associations (from GenCC):

renal tubule disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CCDC158 links:

Genome browser will be placed here

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=-0.88).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0135 (2057/152220) while in subpopulation NFE AF = 0.0162 (1104/68014). AF 95% confidence interval is 0.0154. There are 16 homozygotes in GnomAd4. There are 1014 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC158	NM_001394954.1 link	c.2882+122G>A		intron_variant	Intron 20 of 24	ENST00000682701.1	NP_001381883.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CCDC158	ENST00000682701.1 link	c.2882+122G>A	intron_variant	Intron 20 of 24		NM_001394954.1	ENSP00000507278.1
CCDC158	ENST00000504667.2 link	n.2748+122G>A	intron_variant	Intron 8 of 12	1
CCDC158	ENST00000388914.7 link	c.2870+122G>A	intron_variant	Intron 19 of 23	5		ENSP00000373566.2

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2053

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.0139

AC:

7715

AN:

556140

Hom.:

AF XY:

0.0135

AC XY:

4059

AN XY:

299754

show subpopulations

African (AFR)

AF:

0.0118

AC:

140

AN:

11854

American (AMR)

AF:

0.00353

AC:

AN:

17012

Ashkenazi Jewish (ASJ)

AF:

0.0120

AC:

206

AN:

17194

East Asian (EAS)

AF:

0.0000357

AC:

AN:

28020

South Asian (SAS)

AF:

0.00479

AC:

245

AN:

51168

European-Finnish (FIN)

AF:

0.0238

AC:

1088

AN:

45656

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

3548

European-Non Finnish (NFE)

AF:

0.0159

AC:

5606

AN:

352974

Other (OTH)

AF:

0.0123

AC:

353

AN:

28714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0135

AC:

2057

AN:

152220

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1014

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0118

AC:

491

AN:

41526

American (AMR)

AF:

0.00556

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00476

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0257

AC:

272

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1104

AN:

68014

Other (OTH)

AF:

0.0142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

105

209

314

418

523

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:

0.0158

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.2

(source)

DANN

Benign

0.78

PhyloP100

0.10

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