Genetic Variant CCDC144NL:n.169G>A (chr17-20895995-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000327925.7(CCDC144NL):n.169G>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 0.00163 in 1,609,706 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

CCDC144NL
ENST00000327925.7 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.246

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043634176).

BP6

Variant 17-20895995-C-T is Benign according to our data. Variant chr17-20895995-C-T is described in ClinVar as Benign. ClinVar VariationId is 709931.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 = 0.00745 (1135/152262) while in subpopulation AFR AF = 0.0255 (1059/41524). AF 95% confidence interval is 0.0242. There are 23 homozygotes in GnomAd4. There are 511 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327925.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CCDC144NL	NR_164128.1	n.169G>A	non_coding_transcript_exon	Exon 1 of 4
CCDC144NL-AS1	NR_104185.2	n.362+3563C>T	intron	N/A
CCDC144NL-AS1	NR_160710.1	n.620+3563C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CCDC144NL	ENST00000327925.7	TSL:1	n.169G>A	non_coding_transcript_exon	Exon 1 of 4
CCDC144NL-AS1	ENST00000583962.3	TSL:1	n.424+3563C>T	intron	N/A
CCDC144NL	ENST00000647562.3		n.26G>A	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00743

AC:

1130

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.00225

AC:

557

AN:

247822

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.0280

Gnomad AMR exome

AF:

0.000991

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000896

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.00102

AC:

1487

AN:

1457444

Hom.:

Cov.:

AF XY:

0.000976

AC XY:

707

AN XY:

724566

show subpopulations

African (AFR)

AF:

0.0307

AC:

1022

AN:

33340

American (AMR)

AF:

0.00121

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25924

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39628

South Asian (SAS)

AF:

0.00173

AC:

149

AN:

86026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.000814

AC:

AN:

4914

European-Non Finnish (NFE)

AF:

0.000105

AC:

116

AN:

1109652

Other (OTH)

AF:

0.00231

AC:

139

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00745

AC:

1135

AN:

152262

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0255

AC:

1059

AN:

41524

American (AMR)

AF:

0.00216

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68030

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000334

Hom.:

Bravo

AF:

0.00844

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00290

AC:

352

Asia WGS

AF:

0.00318

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.5

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.25

PrimateAI

Benign

0.45

Polyphen

0.99

ClinPred

0.029

GERP RS

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.041

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over