rs17202345

Positions:

• chr10-59856626-T-C

Variant summary

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

The NM_005436.5(CCDC6):​c.304-3924A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,924 control chromosomes in the GnomAD database, including 5,742 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 0.27 (5742 hom., cov: 32)
• Consequence: CCDC6 NM_005436.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

CCDC6 (HGNC:18782): (coiled-coil domain containing 6) This gene encodes a coiled-coil domain-containing protein. The encoded protein is ubiquitously expressed and may function as a tumor suppressor. A chromosomal rearrangement resulting in the expression of a fusion gene containing a portion of this gene and the intracellular kinase-encoding domain of the ret proto-oncogene is the cause of thyroid papillary carcinoma.[provided by RefSeq, Sep 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 (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC6	NM_005436.5	c.304-3924A>G		intron_variant		ENST00000263102.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC6	ENST00000263102.7	c.304-3924A>G		intron_variant		1	NM_005436.5	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40587 AN: 151806 Hom.: 5739 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.267 AC: 40618 AN: 151924 Hom.: 5742 Cov.: 32 AF XY: 0.261 AC XY: 19364 AN XY: 74256

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.275

Alfa AF: 0.279 Hom.: 2411

Bravo AF: 0.265

Asia WGS AF: 0.126 AC: 438 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	0.16
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs17202345; hg19: chr10-61616384;