Genetic Variant NM_025059.4:c.*978A>G (chr6-151619125-A-G) – 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.*978A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,188 control chromosomes in the GnomAD database, including 569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.070 ( 569 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

CCDC170
NM_025059.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.188

Publications

21 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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC170	NM_025059.4 link	c.*978A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000239374.8	NP_079335.2	Q8IYT3
CCDC170	XM_011536147.3 link	c.*978A>G	3_prime_UTR_variant	Exon 11 of 11		XP_011534449.1
CCDC170	XM_011536148.3 link	c.*978A>G	3_prime_UTR_variant	Exon 10 of 10		XP_011534450.1
CCDC170	XM_047419372.1 link	c.*978A>G	3_prime_UTR_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.*978A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_025059.4	ENSP00000239374.6		Q8IYT3

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10620

AN:

152062

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0702

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.0668

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0782

Gnomad OTH

AF:

0.0912

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0698

AC:

10618

AN:

152180

Hom.:

569

Cov.:

AF XY:

0.0688

AC XY:

5119

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0351

AC:

1457

AN:

41536

American (AMR)

AF:

0.0701

AC:

1072

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

334

AN:

3470

East Asian (EAS)

AF:

0.303

AC:

1570

AN:

5178

South Asian (SAS)

AF:

0.0673

AC:

324

AN:

4814

European-Finnish (FIN)

AF:

0.0265

AC:

281

AN:

10590

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0781

AC:

5312

AN:

67986

Other (OTH)

AF:

0.0917

AC:

194

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

503

1006

1508

2011

2514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0793

Hom.:

1049

Bravo

AF:

0.0730

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Estrogen resistance syndrome

Uncertain:1

Mar 01, 2014

Department of Breast and Endocrine Surgery, Kumamoto University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.67

(source)

DANN

Benign

0.80

PhyloP100

0.19

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over