Genetic Variant NM_001395015.1:c.1613C>T (chr10-32583192-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001395015.1(CCDC7):c.1613C>T(p.Thr538Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,231,126 control chromosomes in the GnomAD database, including 7,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/10 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 0.11 ( 1167 hom., cov: 31)

Exomes 𝑓: 0.10 ( 6319 hom. )

Consequence

CCDC7
NM_001395015.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

6 publications found

Variant links:

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

CCDC7 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CCDC7 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 (MetaRNN=0.0016908348).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC7	NM_001395015.1 link	c.1613C>T	p.Thr538Ile	missense_variant	Exon 18 of 44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2 link	c.1613C>T	p.Thr538Ile	missense_variant	Exon 18 of 44	5	NM_001395015.1	ENSP00000491655.1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17160

AN:

151926

Hom.:

1165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.103

AC:

111082

AN:

1079084

Hom.:

6319

Cov.:

AF XY:

0.103

AC XY:

52588

AN XY:

509430

show subpopulations

African (AFR)

AF:

0.0893

AC:

2048

AN:

22944

American (AMR)

AF:

0.220

AC:

1852

AN:

8410

Ashkenazi Jewish (ASJ)

AF:

0.0875

AC:

1256

AN:

14362

East Asian (EAS)

AF:

0.191

AC:

5041

AN:

26398

South Asian (SAS)

AF:

0.262

AC:

5101

AN:

19478

European-Finnish (FIN)

AF:

0.113

AC:

2429

AN:

21522

Middle Eastern (MID)

AF:

0.146

AC:

424

AN:

2908

European-Non Finnish (NFE)

AF:

0.0953

AC:

87639

AN:

919432

Other (OTH)

AF:

0.121

AC:

5292

AN:

43630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

4910

9820

14731

19641

24551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3864

7728

11592

15456

19320

<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:

0.113

AC:

17175

AN:

152042

Hom.:

1167

Cov.:

AF XY:

0.118

AC XY:

8785

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0873

AC:

3623

AN:

41492

American (AMR)

AF:

0.205

AC:

3129

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0914

AC:

317

AN:

3468

East Asian (EAS)

AF:

0.169

AC:

872

AN:

5168

South Asian (SAS)

AF:

0.268

AC:

1292

AN:

4814

European-Finnish (FIN)

AF:

0.114

AC:

1206

AN:

10556

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0932

AC:

6332

AN:

67962

Other (OTH)

AF:

0.105

AC:

222

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

726

1452

2179

2905

3631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.103

Hom.:

535

Bravo

AF:

0.116

TwinsUK

AF:

0.0893

AC:

331

ALSPAC

AF:

0.104

AC:

399

Asia WGS

AF:

0.223

AC:

776

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.59

(source)

DANN

Benign

0.85

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0017

PhyloP100

-0.81

GERP RS

-2.6

Varity_R

0.031

gMVP

0.011

Splicing

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