chr10-59856626-T-C

Variant names:

• chr10-59856626-T-C
• rs17202345
• NM_005436.5:c.304-3924A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCDC6	NM_005436.5	c.304-3924A>G		intron_variant	Intron 1 of 8	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7	c.304-3924A>G		intron_variant	Intron 1 of 8	1	NM_005436.5	ENSP00000263102.6

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

African (AFR) AF: 0.297 AC: 12277 AN: 41400

American (AMR) AF: 0.211 AC: 3224 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3466

East Asian (EAS) AF: 0.0387 AC: 200 AN: 5164

South Asian (SAS) AF: 0.211 AC: 1017 AN: 4812

European-Finnish (FIN) AF: 0.211 AC: 2223 AN: 10544

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19946 AN: 67970

Other (OTH) AF: 0.275 AC: 578 AN: 2104

Alfa AF: 0.281 Hom.: 3842

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17202345; hg19: chr10-61616384;