1-93183478-A-G

Position:

• chr1-93183478-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_001378204.1(CCDC18):​c.117A>G​(p.Leu39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,595,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: CCDC18 NM_001378204.1 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.859

Genes affected

CCDC18 (HGNC:30370): (coiled-coil domain containing 18)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-93183478-A-G is Benign according to our data. Variant chr1-93183478-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3048946.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC18	NM_001378204.1	c.117A>G	p.Leu39=	synonymous_variant	2/29	ENST00000690025.1	NP_001365133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC18	ENST00000690025.1	c.117A>G	p.Leu39=	synonymous_variant	2/29		NM_001378204.1	ENSP00000510597	P4

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000839

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000379 AC: 90 AN: 237730 Hom.: 0 AF XY: 0.000356 AC XY: 46 AN XY: 129168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.000308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000708

Gnomad NFE exome AF: 0.000617

Gnomad OTH exome AF: 0.000528

GnomAD4 exome AF: 0.000300 AC: 433 AN: 1443600 Hom.: 0 Cov.: 29 AF XY: 0.000340 AC XY: 244 AN XY: 717512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000238

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000681

Gnomad4 NFE exome AF: 0.000344

Gnomad4 OTH exome AF: 0.000168

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74394

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000839

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000631 Hom.: 1

Bravo AF: 0.000242

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CCDC18-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.7
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs202201009; hg19: chr1-93649035;