rs3757317

Variant names:

• chr6-151544396-C-T
• rs3757317
• NM_025059.4:c.444-176C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025059.4(CCDC170):​c.444-176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,150 control chromosomes in the GnomAD database, including 1,599 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 0.13 (1599 hom., cov: 32)
• Consequence: CCDC170 NM_025059.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 7 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC170	NM_025059.4	c.444-176C>T		intron_variant	Intron 3 of 10	ENST00000239374.8	NP_079335.2
CCDC170	XM_011536147.3	c.462-176C>T		intron_variant	Intron 3 of 10		XP_011534449.1
CCDC170	XM_011536148.3	c.462-176C>T		intron_variant	Intron 3 of 9		XP_011534450.1
CCDC170	XM_047419372.1	c.444-176C>T		intron_variant	Intron 3 of 9		XP_047275328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8	c.444-176C>T		intron_variant	Intron 3 of 10	1	NM_025059.4	ENSP00000239374.6
CCDC170	ENST00000544131.1	n.434-176C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20305 AN: 152032 Hom.: 1595 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20321 AN: 152150 Hom.: 1599 Cov.: 32 AF XY: 0.133 AC XY: 9910 AN XY: 74388

African (AFR) AF: 0.0546 AC: 2267 AN: 41514

American (AMR) AF: 0.139 AC: 2126 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1413 AN: 5160

South Asian (SAS) AF: 0.175 AC: 844 AN: 4820

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11467 AN: 67988

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.159 Hom.: 2564

Bravo AF: 0.132

Asia WGS AF: 0.211 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		-1.0
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: rs3757317; hg19: chr6-151865531; COSMIC: COSV53342946;