NM_005436.5:c.304-22334G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.97).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• 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

African (AFR) AF: 0.00460 AC: 191 AN: 41524

American (AMR) AF: 0.0130 AC: 199 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00496 AC: 24 AN: 4834

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1468 AN: 67998

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.00382 Hom.: 2096

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1624715; hg19: chr10-61634794;