Genetic Variant CCDC170:p.Val683Ile (chr6-151618046-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025059.4(CCDC170):c.2047G>A(p.Val683Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,698 control chromosomes in the GnomAD database, including 221,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.56 ( 25445 hom., cov: 30)

Exomes 𝑓: 0.51 ( 195643 hom. )

Consequence

CCDC170
NM_025059.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

48 publications found

Variant links:

Genes affected

CCDC170 (HGNC:21177): (coiled-coil domain containing 170) The function of this gene and its encoded protein is not known. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and bone mineral density, but no link to this specific gene has been found. [provided by RefSeq, May 2010]

CCDC170 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=7.107187E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC170	NM_025059.4 link	c.2047G>A	p.Val683Ile	missense_variant	Exon 11 of 11	ENST00000239374.8	NP_079335.2	Q8IYT3
CCDC170	XM_011536147.3 link	c.2065G>A	p.Val689Ile	missense_variant	Exon 11 of 11		XP_011534449.1
CCDC170	XM_011536148.3 link	c.1864G>A	p.Val622Ile	missense_variant	Exon 10 of 10		XP_011534450.1
CCDC170	XM_047419372.1 link	c.1846G>A	p.Val616Ile	missense_variant	Exon 10 of 10		XP_047275328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8 link	c.2047G>A	p.Val683Ile	missense_variant	Exon 11 of 11	1	NM_025059.4	ENSP00000239374.6		Q8IYT3

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85656

AN:

151842

Hom.:

25413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.488

AC:

121553

AN:

249294

AF XY:

0.493

show subpopulations

Gnomad AFR exome

AF:

0.750

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.513

AC:

750021

AN:

1461736

Hom.:

195643

Cov.:

AF XY:

0.514

AC XY:

373535

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.754

AC:

25239

AN:

33476

American (AMR)

AF:

0.314

AC:

14039

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

14922

AN:

26136

East Asian (EAS)

AF:

0.396

AC:

15729

AN:

39700

South Asian (SAS)

AF:

0.509

AC:

43933

AN:

86254

European-Finnish (FIN)

AF:

0.455

AC:

24279

AN:

53408

Middle Eastern (MID)

AF:

0.626

AC:

3609

AN:

5766

European-Non Finnish (NFE)

AF:

0.518

AC:

575942

AN:

1111898

Other (OTH)

AF:

0.535

AC:

32329

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19385

38770

58156

77541

96926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16606

33212

49818

66424

83030

<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:

0.564

AC:

85730

AN:

151962

Hom.:

25445

Cov.:

AF XY:

0.556

AC XY:

41279

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.750

AC:

31098

AN:

41452

American (AMR)

AF:

0.433

AC:

6613

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1973

AN:

3466

East Asian (EAS)

AF:

0.415

AC:

2141

AN:

5154

South Asian (SAS)

AF:

0.496

AC:

2376

AN:

4792

European-Finnish (FIN)

AF:

0.451

AC:

4756

AN:

10550

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35047

AN:

67958

Other (OTH)

AF:

0.582

AC:

1231

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1812

3623

5435

7246

9058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.538

Hom.:

78345

Bravo

AF:

0.570

TwinsUK

AF:

0.516

AC:

1914

ALSPAC

AF:

0.512

AC:

1975

ESP6500AA

AF:

0.756

AC:

3060

ESP6500EA

AF:

0.534

AC:

4451

ExAC

AF:

0.498

AC:

60179

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

EpiCase

AF:

0.531

EpiControl

AF:

0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.2

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.17

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.8

PhyloP100

1.6

PrimateAI

Benign

0.42

PROVEAN

Benign

0.50

REVEL

Benign

0.044

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.030

MPC

0.091

ClinPred

0.0011

GERP RS

3.5

Varity_R

0.020

gMVP

0.090

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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