Genetic Variant CCDC144NL:n.345G>A (chr17-20895813-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000327925.6(CCDC144NL):n.345G>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 0.00113 in 1,613,502 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 12 hom. )

Consequence

CCDC144NL
ENST00000327925.6 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.246

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=0.004626602).

BP6

Variant 17-20895813-C-T is Benign according to our data. Variant chr17-20895813-C-T is described in ClinVar as [Benign]. Clinvar id is 785562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00621 (945/152236) while in subpopulation AFR AF= 0.0218 (905/41522). AF 95% confidence interval is 0.0206. There are 17 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CCDC144NL	NR_164128.1 link	n.351G>A	non_coding_transcript_exon_variant	Exon 1 of 4
CCDC144NL-AS1	NR_104185.2 link	n.362+3381C>T	intron_variant	Intron 2 of 2
CCDC144NL-AS1	NR_160710.1 link	n.620+3381C>T	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CCDC144NL	ENST00000327925.6 link	n.345G>A	non_coding_transcript_exon_variant	Exon 1 of 4	1
CCDC144NL-AS1	ENST00000583962.2 link	n.369+3381C>T	intron_variant	Intron 2 of 2	1
CCDC144NL	ENST00000647562.3 link	n.208G>A	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00621

AC:

945

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00153

AC:

384

AN:

251048

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000598

AC:

874

AN:

1461266

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

377

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00621

AC:

945

AN:

152236

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

436

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00688

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00194

AC:

235

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

- -

Jan 30, 2018

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

0.27

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.3

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.54

Polyphen

0.99

ClinPred

0.015

Varity_R

0.14

gMVP

0.030

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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