Genetic Variant CCDC144NL:n.253A>G (chr17-20895905-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000327925.6(CCDC144NL):n.253A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,612,376 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 11 hom. )

Consequence

CCDC144NL
ENST00000327925.6 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

CCDC144NL (HGNC:):

CCDC144NL links:

CCDC144NL-AS1 (HGNC:51340): (CCDC144NL antisense RNA 1)

CCDC144NL-AS1 links:

CCDC144NL (HGNC:33735): (CCDC144A N-terminal like (pseudogene))

CCDC144NL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054231584).

BP6

Variant 17-20895905-T-C is Benign according to our data. Variant chr17-20895905-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 773068.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CCDC144NL	NR_164128.1 link	n.259A>G	non_coding_transcript_exon_variant	Exon 1 of 4
CCDC144NL-AS1	NR_104185.2 link	n.362+3473T>C	intron_variant	Intron 2 of 2
CCDC144NL-AS1	NR_160710.1 link	n.620+3473T>C	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CCDC144NL	ENST00000327925.6 link	n.253A>G	non_coding_transcript_exon_variant	Exon 1 of 4	1
CCDC144NL-AS1	ENST00000583962.2 link	n.369+3473T>C	intron_variant	Intron 2 of 2	1
CCDC144NL	ENST00000647562.3 link	n.116A>G	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

177

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00137

AC:

343

AN:

250862

Hom.:

AF XY:

0.00141

AC XY:

191

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00207

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00140

AC:

2047

AN:

1460292

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1064

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.000694

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152084

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00170

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00156

AC:

190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.9

DANN

Benign

0.31

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.35

M_CAP

Benign

0.00070

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.81

PrimateAI

Uncertain

0.49

Polyphen

0.0

ClinPred

0.00059

GERP RS

-1.3

Varity_R

0.067

gMVP

0.044

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