Genetic Variant CCDC144NL:n.384G>A (chr17-20895774-C-T) – 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.384G>A 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 0.00731 in 1,613,506 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 44 hom. )

Consequence

CCDC144NL
ENST00000327925.6 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.121

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=0.007117778).

BP6

Variant 17-20895774-C-T is Benign according to our data. Variant chr17-20895774-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647571.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CCDC144NL	NR_164128.1 link	n.390G>A	non_coding_transcript_exon_variant	Exon 1 of 4
CCDC144NL-AS1	NR_104185.2 link	n.362+3342C>T	intron_variant	Intron 2 of 2
CCDC144NL-AS1	NR_160710.1 link	n.620+3342C>T	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CCDC144NL	ENST00000327925.6 link	n.384G>A	non_coding_transcript_exon_variant	Exon 1 of 4	1
CCDC144NL-AS1	ENST00000583962.2 link	n.369+3342C>T	intron_variant	Intron 2 of 2	1
CCDC144NL	ENST00000647562.3 link	n.247G>A	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00677

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00780

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00489

AC:

1226

AN:

250756

Hom.:

AF XY:

0.00514

AC XY:

697

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00596

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00753

AC:

10999

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

5407

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00391

Gnomad4 FIN exome

AF:

0.00627

Gnomad4 NFE exome

AF:

0.00880

Gnomad4 OTH exome

AF:

0.00590

GnomAD4 genome

AF:

0.00524

AC:

798

AN:

152272

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

386

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00677

Gnomad4 NFE

AF:

0.00781

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00658

Hom.:

Bravo

AF:

0.00487

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00886

AC:

ExAC

AF:

0.00460

AC:

559

EpiCase

AF:

0.00720

EpiControl

AF:

0.00741

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CCDC144NL: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.1

DANN

Benign

0.94

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.63

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.22

PrimateAI

Uncertain

0.54

Polyphen

0.33

ClinPred

0.0016

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.14

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