10-59821209-A-G

Position:

• chr10-59821209-A-G

Variant summary

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

The NM_005436.5(CCDC6):​c.583-6454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,336 control chromosomes in the GnomAD database, including 70,193 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 0.96 (70193 hom., cov: 32)
• Consequence: CCDC6 NM_005436.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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 (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC6	NM_005436.5	c.583-6454T>C		intron_variant		ENST00000263102.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC6	ENST00000263102.7	c.583-6454T>C		intron_variant		1	NM_005436.5	P1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 146046 AN: 152218 Hom.: 70130 Cov.: 32

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.960 AC: 146168 AN: 152336 Hom.: 70193 Cov.: 32 AF XY: 0.961 AC XY: 71589 AN XY: 74492

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.963

Alfa AF: 0.942 Hom.: 30289

Bravo AF: 0.963

Asia WGS AF: 0.994 AC: 3457 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	0.68
DANN	Benign	0.59

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: rs920964; hg19: chr10-61580967;