rs6929137

Variant names:

Variant summary

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

The NM_025059.4(CCDC170):c.1810G>A(p.Val604Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,613,434 control chromosomes in the GnomAD database, including 89,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.36 ( 10415 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79392 hom. )

Consequence

CCDC170
NM_025059.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:1

Conservation

PhyloP100: 0.969

Publications

96 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:

ENSG00000300966 (HGNC:):

ENSG00000300966 links:

RNU6-813P (HGNC:47776): (RNA, U6 small nuclear 813, pseudogene)

RNU6-813P 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=2.2158027E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC170	NM_025059.4 link	c.1810G>A	p.Val604Ile	missense_variant	Exon 10 of 11	ENST00000239374.8	NP_079335.2	Q8IYT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8 link	c.1810G>A	p.Val604Ile	missense_variant	Exon 10 of 11	1	NM_025059.4	ENSP00000239374.6		Q8IYT3

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54147

AN:

151926

Hom.:

10397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.308

AC:

76889

AN:

249358

AF XY:

0.311

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.325

AC:

475628

AN:

1461390

Hom.:

79392

Cov.:

AF XY:

0.326

AC XY:

236981

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.498

AC:

16678

AN:

33478

American (AMR)

AF:

0.207

AC:

9259

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

9478

AN:

26120

East Asian (EAS)

AF:

0.280

AC:

11118

AN:

39670

South Asian (SAS)

AF:

0.333

AC:

28751

AN:

86244

European-Finnish (FIN)

AF:

0.192

AC:

10270

AN:

53410

Middle Eastern (MID)

AF:

0.393

AC:

2267

AN:

5766

European-Non Finnish (NFE)

AF:

0.330

AC:

367112

AN:

1111604

Other (OTH)

AF:

0.343

AC:

20695

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16690

33379

50069

66758

83448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11986

23972

35958

47944

59930

<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:

0.356

AC:

54199

AN:

152044

Hom.:

10415

Cov.:

AF XY:

0.348

AC XY:

25889

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.499

AC:

20671

AN:

41446

American (AMR)

AF:

0.272

AC:

4159

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1244

AN:

3466

East Asian (EAS)

AF:

0.319

AC:

1647

AN:

5168

South Asian (SAS)

AF:

0.329

AC:

1583

AN:

4810

European-Finnish (FIN)

AF:

0.177

AC:

1874

AN:

10570

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21880

AN:

67990

Other (OTH)

AF:

0.367

AC:

776

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.339

Hom.:

36861

Bravo

AF:

0.370

TwinsUK

AF:

0.328

AC:

1215

ALSPAC

AF:

0.331

AC:

1277

ESP6500AA

AF:

0.495

AC:

1842

ESP6500EA

AF:

0.328

AC:

2695

ExAC

AF:

0.317

AC:

38302

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.336

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Estrogen resistance syndrome

Pathogenic:1

Mar 01, 2014

Department of Breast and Endocrine Surgery, Kumamoto University

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

CCDC170-related condition

Uncertain:1

Apr 24, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

not specified

Benign:1

Oct 28, 2020

H3Africa Consortium

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.51, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.71

MetaRNN

Benign

0.00022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.97

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

REVEL

Benign

0.044

Sift

Benign

0.36

Sift4G

Benign

0.22

Polyphen

0.026

Vest4

0.018

MPC

0.096

ClinPred

0.0057

GERP RS

3.4

Varity_R

0.022

gMVP

0.072

Mutation Taster

=96/4

disease causing (ClinVar)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over