18-68838809-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024781.3(CCDC102B):c.710C>G(p.Thr237Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,613,832 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T237M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0089 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (15 hom.)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0740

Genes affected

CCDC102B (HGNC:26295): (coiled-coil domain containing 102B)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029851794).
• BP6: Variant 18-68838809-C-G is Benign according to our data. Variant chr18-68838809-C-G is described in ClinVar as [Benign]. Clinvar id is 768940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00887 (1349/152104) while in subpopulation AFR AF= 0.0308 (1279/41480). AF 95% confidence interval is 0.0294. There are 21 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC102B	NM_024781.3	c.710C>G	p.Thr237Arg	missense_variant	3/8	ENST00000360242.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC102B	ENST00000360242.9	c.710C>G	p.Thr237Arg	missense_variant	3/8	1	NM_024781.3	P2
CCDC102B	ENST00000584156.5	c.710C>G	p.Thr237Arg	missense_variant	2/6	1		A2
CCDC102B	ENST00000584775.5	c.710C>G	p.Thr237Arg	missense_variant	5/7	1
CCDC102B	ENST00000577772.5	n.768C>G		non_coding_transcript_exon_variant	3/7	2

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1350 AN: 151986 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00209 AC: 525 AN: 251260 Hom.: 3 AF XY: 0.00155 AC XY: 211 AN XY: 135792

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000982 AC: 1436 AN: 1461728 Hom.: 15 Cov.: 31 AF XY: 0.000840 AC XY: 611 AN XY: 727158

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.00887 AC: 1349 AN: 152104 Hom.: 21 Cov.: 32 AF XY: 0.00853 AC XY: 634 AN XY: 74342

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.00334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.000538 Hom.: 0

Bravo AF: 0.0103

ESP6500AA AF: 0.0268 AC: 118

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00258 AC: 313

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.22
Dann	Benign	0.46
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.23	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.065	.;B;.
Vest4		0.11, 0.12
MVP		0.15
MPC		0.013
ClinPred		0.00071	T
GERP RS		-0.74
Varity_R		0.043
gMVP		0.052

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: rs75713049; hg19: chr18-66506046;