rs1624715

chr10-59875036-C-Achr10-59875036-C-Gchr10-59875036-C-T

Variant summary

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

The NM_005436.5(CCDC6):c.304-22334G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,196 control chromosomes in the GnomAD database, including 44,257 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 0.76 (44257 hom., cov: 33)
• Consequence: CCDC6 NM_005436.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC6	NM_005436.5	c.304-22334G>T		intron_variant		ENST00000263102.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC6	ENST00000263102.7	c.304-22334G>T		intron_variant		1	NM_005436.5	P1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115619 AN: 152078 Hom.: 44204 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.760 AC: 115733 AN: 152196 Hom.: 44257 Cov.: 33 AF XY: 0.765 AC XY: 56925 AN XY: 74424

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.742

Alfa AF: 0.676 Hom.: 1847

Bravo AF: 0.777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.13
Dann	Benign	0.66

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: rs1624715; hg19: chr10-61634794;