Variant 14-57480703-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BS1BS2

The NM_018168.4(CCDC198):c.547C>T(p.Gln183Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,613,932 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 45 hom., cov: 32)

Exomes 𝑓: 0.032 ( 851 hom. )

Consequence

CCDC198
NM_018168.4 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

CCDC198 (HGNC:20189): (coiled-coil domain containing 198)

CCDC198 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM4

Stoplost variant in NM_018168.4 Downstream stopcodon found after 8 codons.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3379/152206) while in subpopulation NFE AF= 0.0349 (2374/67986). AF 95% confidence interval is 0.0337. There are 45 homozygotes in gnomad4. There are 1605 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC198	NM_018168.4 linkuse as main transcript	c.547C>T	p.Gln183Ter	stop_gained	5/6	ENST00000216445.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC198	ENST00000216445.8 linkuse as main transcript	c.547C>T	p.Gln183Ter	stop_gained	5/6	1	NM_018168.4	A1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3383

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0349

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0242

AC:

6096

AN:

251384

Hom.:

AF XY:

0.0257

AC XY:

3491

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00529

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0360

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0322

AC:

47139

AN:

1461726

Hom.:

851

Cov.:

AF XY:

0.0321

AC XY:

23369

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00541

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0234

Gnomad4 FIN exome

AF:

0.0295

Gnomad4 NFE exome

AF:

0.0368

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0222

AC:

3379

AN:

152206

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1605

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00621

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0275

Gnomad4 NFE

AF:

0.0349

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0300

Hom.:

109

Bravo

AF:

0.0209

TwinsUK

AF:

0.0386

AC:

143

ALSPAC

AF:

0.0340

AC:

131

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0352

AC:

303

ExAC

AF:

0.0256

AC:

3113

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0358

EpiControl

AF:

0.0373

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 06, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.58

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.89

MutationTaster

Benign

1.0

A;A;A

Vest4

0.14

GERP RS

4.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over