rs6929137

Positions:

• chr6-151615542-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: 0.969

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]

LOC107986528 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CCDC170	NM_025059.4	c.1810G>A	p.Val604Ile	missense_variant	10/11	ENST00000239374.8	NP_079335.2
LOC107986528	XR_001743865.2	n.105+1179C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8	c.1810G>A	p.Val604Ile	missense_variant	10/11	1	NM_025059.4	ENSP00000239374	P1
CCDC170	ENST00000537358.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54147 AN: 151926 Hom.: 10397 Cov.: 32

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

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.: 35 AF XY: 0.326 AC XY: 236981 AN XY: 727036

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.: 32 AF XY: 0.348 AC XY: 25889 AN XY: 74314

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:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Estrogen resistance syndrome Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Department of Breast and Endocrine Surgery, Kumamoto University

Mar 01, 2014

- -

not specified Benign:1

Benign, criteria provided, single submitter

research

H3Africa Consortium

Oct 28, 2020

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	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.099	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.044
Sift	Benign	0.36	T
Sift4G	Benign	0.22	T
Polyphen		0.026	B
Vest4		0.018
MPC		0.096
ClinPred		0.0057	T
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

Other links and lift over

dbSNP: rs6929137; hg19: chr6-151936677; COSMIC: COSV53337542; COSMIC: COSV53337542;