10-59875036-C-T

Variant names:

• chr10-59875036-C-T
• rs1624715
• NM_005436.5:c.304-22334G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005436.5(CCDC6):​c.304-22334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 152,232 control chromosomes in the GnomAD database, including 21 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 0.014 (21 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=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (2076/152232) while in subpopulation NFE AF= 0.0216 (1468/67998). AF 95% confidence interval is 0.0207. There are 21 homozygotes in gnomad4. There are 933 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2076 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC6	NM_005436.5	c.304-22334G>A		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.304-22334G>A		intron_variant	Intron 1 of 8	1	NM_005436.5	ENSP00000263102.6

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2079 AN: 152114 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0136 AC: 2076 AN: 152232 Hom.: 21 Cov.: 33 AF XY: 0.0125 AC XY: 933 AN XY: 74444

Gnomad4 AFR AF: 0.00460

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00423 Hom.: 1847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.71

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;