Genetic Variant CCDC144NL:n.352T>C (chr17-20895806-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000327925.6(CCDC144NL):n.352T>C 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 0.494 in 1,593,096 control chromosomes in the GnomAD database, including 199,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22523 hom., cov: 32)

Exomes 𝑓: 0.49 ( 176886 hom. )

Consequence

CCDC144NL
ENST00000327925.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.376

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.401482E-6).

BP6

Variant 17-20895806-A-G is Benign according to our data. Variant chr17-20895806-A-G is described in ClinVar as [Benign]. Clinvar id is 769432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CCDC144NL	NR_164128.1 link	n.358T>C	non_coding_transcript_exon_variant	Exon 1 of 4
CCDC144NL-AS1	NR_104185.2 link	n.362+3374A>G	intron_variant	Intron 2 of 2
CCDC144NL-AS1	NR_160710.1 link	n.620+3374A>G	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CCDC144NL	ENST00000327925.6 link	n.352T>C	non_coding_transcript_exon_variant	Exon 1 of 4	1
CCDC144NL-AS1	ENST00000583962.2 link	n.369+3374A>G	intron_variant	Intron 2 of 2	1
CCDC144NL	ENST00000647562.3 link	n.215T>C	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81756

AN:

151764

Hom.:

22502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.525

GnomAD3 exomes

AF:

0.489

AC:

118148

AN:

241420

Hom.:

30401

AF XY:

0.484

AC XY:

63046

AN XY:

130296

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.487

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.490

AC:

705909

AN:

1441214

Hom.:

176886

Cov.:

AF XY:

0.488

AC XY:

349265

AN XY:

716230

show subpopulations

Gnomad4 AFR exome

AF:

0.678

Gnomad4 AMR exome

AF:

0.477

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.510

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.539

AC:

81821

AN:

151882

Hom.:

22523

Cov.:

AF XY:

0.536

AC XY:

39802

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.672

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.472

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.443

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.489

Gnomad4 OTH

AF:

0.526

Alfa

AF:

0.497

Hom.:

6465

Bravo

AF:

0.542

ExAC

AF:

0.489

AC:

59330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.024

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.1

DANN

Benign

0.45

DEOGEN2

Benign

0.00095

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00080

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0000024

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.9

PrimateAI

Uncertain

0.51

Polyphen

0.0

ClinPred

0.0017

GERP RS

-1.3

Varity_R

0.072

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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