rs3734804

chr6-151618046-G-Achr6-151618046-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (25445 hom., cov: 30)
  • Exomes 𝑓: 0.51 (195643 hom.)
• Consequence: CCDC170 NM_025059.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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]

ACMG classification

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/exons	MANE	UniProt
CCDC170	NM_025059.4	c.2047G>A	p.Val683Ile	missense_variant	11/11	ENST00000239374.8
CCDC170	XM_011536147.3	c.2065G>A	p.Val689Ile	missense_variant	11/11
CCDC170	XM_011536148.3	c.1864G>A	p.Val622Ile	missense_variant	10/10
CCDC170	XM_047419372.1	c.1846G>A	p.Val616Ile	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8	c.2047G>A	p.Val683Ile	missense_variant	11/11	1	NM_025059.4	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85656 AN: 151842 Hom.: 25413 Cov.: 30

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

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.: 50 AF XY: 0.514 AC XY: 373535 AN XY: 727180

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.: 30 AF XY: 0.556 AC XY: 41279 AN XY: 74262

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	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.2
Dann	Benign	0.64
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.8	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.044
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.030
MPC		0.091
ClinPred		0.0011	T
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

Other links and lift over

dbSNP: rs3734804; hg19: chr6-151939181; COSMIC: COSV53344090; COSMIC: COSV53344090;