rs3757318

chr6-151592978-G-A

Variant summary

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

The NM_025059.4(CCDC170):c.1294-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 963,046 control chromosomes in the GnomAD database, including 3,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (450 hom., cov: 32)
  • Exomes 𝑓: 0.078 (3122 hom.)
• Consequence: CCDC170 NM_025059.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC170	NM_025059.4	c.1294-129G>A		intron_variant		ENST00000239374.8
CCDC170	XM_011536147.3	c.1312-129G>A		intron_variant
CCDC170	XM_011536148.3	c.1111-129G>A		intron_variant
CCDC170	XM_047419372.1	c.1093-129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8	c.1294-129G>A		intron_variant		1	NM_025059.4	P1
CCDC170	ENST00000537358.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9751 AN: 152146 Hom.: 449 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0774

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0860

GnomAD4 exome AF: 0.0775 AC: 62839 AN: 810782 Hom.: 3122 Cov.: 11 AF XY: 0.0776 AC XY: 32031 AN XY: 412778

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.0487

Gnomad4 ASJ exome AF: 0.0809

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.0593

Gnomad4 FIN exome AF: 0.0340

Gnomad4 NFE exome AF: 0.0756

Gnomad4 OTH exome AF: 0.0849

GnomAD4 genome AF: 0.0641 AC: 9753 AN: 152264 Hom.: 450 Cov.: 32 AF XY: 0.0629 AC XY: 4681 AN XY: 74456

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.0774

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.0805 Hom.: 1343

Bravo AF: 0.0673

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.014
Dann	Benign	0.24

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: rs3757318; hg19: chr6-151914113; COSMIC: COSV53337009; COSMIC: COSV53337009;