dbSNP rs3734804: CCDC170:p.Val683Ile (chr6-151618046-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.488

AC:

121553

AN:

249294

Hom.:

31334

AF XY:

0.493

AC XY:

66703

AN XY:

135256

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 SAS exome

AF:

0.504

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

Gnomad4 AFR exome

AF:

0.754

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.509

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.518

Gnomad4 OTH exome

AF:

0.535

GnomAD4 genome

AF:

0.564

AC:

85730

AN:

151962

Hom.:

25445

Cov.:

AF XY:

0.556

AC XY:

41279

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.433

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.516

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.532

Hom.:

48088

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over