6-151618046-G-A

Variant names:

• chr6-151618046-G-A
• rs3734804
• NM_025059.4:c.2047G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC170	NM_025059.4	MANE Select	c.2047G>A	p.Val683Ile	missense	Exon 11 of 11	NP_079335.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC170	ENST00000239374.8	TSL:1 MANE Select	c.2047G>A	p.Val683Ile	missense	Exon 11 of 11	ENSP00000239374.6	Q8IYT3
	CCDC170	ENST00000867015.1		c.2026G>A	p.Val676Ile	missense	Exon 11 of 11	ENSP00000537074.1
	CCDC170	ENST00000867016.1		c.1918G>A	p.Val640Ile	missense	Exon 10 of 10	ENSP00000537075.1

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

GnomAD2 exomes AF: 0.488 AC: 121553 AN: 249294 AF XY: 0.493

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 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

African (AFR) AF: 0.754 AC: 25239 AN: 33476

American (AMR) AF: 0.314 AC: 14039 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 14922 AN: 26136

East Asian (EAS) AF: 0.396 AC: 15729 AN: 39700

South Asian (SAS) AF: 0.509 AC: 43933 AN: 86254

European-Finnish (FIN) AF: 0.455 AC: 24279 AN: 53408

Middle Eastern (MID) AF: 0.626 AC: 3609 AN: 5766

European-Non Finnish (NFE) AF: 0.518 AC: 575942 AN: 1111898

Other (OTH) AF: 0.535 AC: 32329 AN: 60386

GnomAD4 genome AF: 0.564 AC: 85730 AN: 151962 Hom.: 25445 Cov.: 30 AF XY: 0.556 AC XY: 41279 AN XY: 74262

African (AFR) AF: 0.750 AC: 31098 AN: 41452

American (AMR) AF: 0.433 AC: 6613 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3466

East Asian (EAS) AF: 0.415 AC: 2141 AN: 5154

South Asian (SAS) AF: 0.496 AC: 2376 AN: 4792

European-Finnish (FIN) AF: 0.451 AC: 4756 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35047 AN: 67958

Other (OTH) AF: 0.582 AC: 1231 AN: 2114

Alfa AF: 0.538 Hom.: 78345

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 v4.9

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
PhyloP100		1.6
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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