rs3734805

Positions:

• chr6-151618215-A-C
• chr6-151618215-A-T

Variant summary

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

The NM_025059.4(CCDC170):​c.*68A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,341,036 control chromosomes in the GnomAD database, including 5,350 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 0.073 (588 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4762 hom.)
• Consequence: CCDC170 NM_025059.4 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.00500

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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC170	NM_025059.4	c.*68A>C		3_prime_UTR_variant	11/11	ENST00000239374.8	NP_079335.2
CCDC170	XM_011536147.3	c.*68A>C		3_prime_UTR_variant	11/11		XP_011534449.1
CCDC170	XM_011536148.3	c.*68A>C		3_prime_UTR_variant	10/10		XP_011534450.1
CCDC170	XM_047419372.1	c.*68A>C		3_prime_UTR_variant	10/10		XP_047275328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8	c.*68A>C		3_prime_UTR_variant	11/11	1	NM_025059.4	ENSP00000239374	P1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11060 AN: 152116 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0924

GnomAD4 exome AF: 0.0794 AC: 94405 AN: 1188802 Hom.: 4762 Cov.: 15 AF XY: 0.0791 AC XY: 47217 AN XY: 596630

Gnomad4 AFR exome AF: 0.0433

Gnomad4 AMR exome AF: 0.0526

Gnomad4 ASJ exome AF: 0.0969

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.0600

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0771

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.0726 AC: 11058 AN: 152234 Hom.: 588 Cov.: 32 AF XY: 0.0714 AC XY: 5313 AN XY: 74424

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.0962

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.0929

Alfa AF: 0.0872 Hom.: 1609

Bravo AF: 0.0767

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Estrogen resistance syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

research

Department of Breast and Endocrine Surgery, Kumamoto University

Mar 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.51

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: rs3734805; hg19: chr6-151939350; COSMIC: COSV53337016; COSMIC: COSV53337016;