chr1-93264899-A-G

Variant names:

• chr1-93264899-A-G
• NM_001378204.1:c.3883A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378204.1(CCDC18):​c.3883A>G​(p.Lys1295Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000712 in 1,404,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CCDC18 NM_001378204.1 missense, splice_region
• Scores: Splicing: ADA: 0.6893
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

Genes affected

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

CCDC18-AS1 (HGNC:52262): (CCDC18 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3436546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378204.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC18	NM_001378204.1	MANE Select	c.3883A>G	p.Lys1295Glu	missense splice_region	Exon 27 of 29	NP_001365133.1	A0A8I5KWA2
	CCDC18	NM_001306076.1		c.3880A>G	p.Lys1294Glu	missense splice_region	Exon 27 of 29	NP_001293005.1	Q6PH87
	CCDC18	NM_206886.4		c.3883A>G	p.Lys1295Glu	missense splice_region	Exon 27 of 28	NP_996769.3	Q6PH87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC18	ENST00000690025.1	MANE Select	c.3883A>G	p.Lys1295Glu	missense splice_region	Exon 27 of 29	ENSP00000510597.1	A0A8I5KWA2
	CCDC18	ENST00000401026.7	TSL:1	c.3883A>G	p.Lys1295Glu	missense splice_region	Exon 27 of 28	ENSP00000383808.3	E9PFB9
	CCDC18	ENST00000447456.1	TSL:1	n.639A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404724 Hom.: 0 Cov.: 25 AF XY: 0.00000142 AC XY: 1 AN XY: 701886

African (AFR) AF: 0.00 AC: 0 AN: 32458

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060190

Other (OTH) AF: 0.00 AC: 0 AN: 58400

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.036	D
Vest4		0.52
MVP		0.43
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.64
gMVP		0.63
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.69
dbscSNV1_RF	Benign	0.53
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

hg19: chr1-93730456;