rs139422966

Variant names:

• chr1-93264823-T-A
• rs139422966
• NM_001378204.1:c.3807T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-93264823-T-A
• chr1-93264823-T-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001378204.1(CCDC18):​c.3807T>A​(p.Asp1269Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,613,582 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: CCDC18 NM_001378204.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.491
• Publications: 1 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00622496).
• BP6: Variant 1-93264823-T-A is Benign according to our data. Variant chr1-93264823-T-A is described in ClinVar as Benign. ClinVar VariationId is 3040891.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.3807T>A	p.Asp1269Glu	missense	Exon 27 of 29	NP_001365133.1	A0A8I5KWA2
	CCDC18	NM_001306076.1		c.3804T>A	p.Asp1268Glu	missense	Exon 27 of 29	NP_001293005.1	Q6PH87
	CCDC18	NM_206886.4		c.3807T>A	p.Asp1269Glu	missense	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.3807T>A	p.Asp1269Glu	missense	Exon 27 of 29	ENSP00000510597.1	A0A8I5KWA2
	CCDC18	ENST00000401026.7	TSL:1	c.3807T>A	p.Asp1269Glu	missense	Exon 27 of 28	ENSP00000383808.3	E9PFB9
	CCDC18	ENST00000447456.1	TSL:1	n.563T>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 305 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00688

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000445 AC: 111 AN: 249172 AF XY: 0.000348

Gnomad AFR exome AF: 0.00665

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000198 AC: 289 AN: 1461268 Hom.: 1 Cov.: 30 AF XY: 0.000158 AC XY: 115 AN XY: 726986

African (AFR) AF: 0.00702 AC: 235 AN: 33462

American (AMR) AF: 0.000335 AC: 15 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111598

Other (OTH) AF: 0.000480 AC: 29 AN: 60362

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152314 Hom.: 2 Cov.: 32 AF XY: 0.00193 AC XY: 144 AN XY: 74476

African (AFR) AF: 0.00700 AC: 291 AN: 41576

American (AMR) AF: 0.000719 AC: 11 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000692 Hom.: 0

Bravo AF: 0.00201

ESP6500AA AF: 0.00673 AC: 25

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000629 AC: 76

Asia WGS AF: 0.000289 AC: 1 AN: 3474

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCDC18-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.49
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	0.51	T
Vest4		0.17
MVP		0.39
ClinPred		0.063	T
GERP RS		-1.9
Varity_R		0.030
gMVP		0.056
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139422966; hg19: chr1-93730380;