Variant 6-151615542-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

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

Exomes 𝑓: 0.33 ( 79392 hom. )

Consequence

CCDC170
NM_025059.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 0.969

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:

LOC107986528 (HGNC:):

LOC107986528 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2158027E-4).

BP6

Variant 6-151615542-G-A is Benign according to our data. Variant chr6-151615542-G-A is described in ClinVar as [Benign]. Clinvar id is 155873.Status of the report is criteria_provided_single_submitter, 1 stars.

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
CCDC170	ENST00000537358.1 link	n.*22G>A		downstream_gene_variant		3

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

GnomAD3 exomes

AF:

0.308

AC:

76889

AN:

249358

Hom.:

12736

AF XY:

0.311

AC XY:

42139

AN XY:

135294

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 SAS exome

AF:

0.330

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

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.356

AC:

54199

AN:

152044

Hom.:

10415

Cov.:

AF XY:

0.348

AC XY:

25889

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.339

Hom.:

17134

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: Benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

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

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over