Genetic Variant NM_018704.3:c.330+68G>T (chr1-112449240-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018704.3(CTTNBP2NL):c.330+68G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 891,622 control chromosomes in the GnomAD database, including 27,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4092 hom., cov: 29)

Exomes 𝑓: 0.24 ( 23296 hom. )

Consequence

CTTNBP2NL
NM_018704.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.326

Publications

10 publications found

Variant links:

Genes affected

CTTNBP2NL (HGNC:25330): (CTTNBP2 N-terminal like) Enables protein phosphatase 2A binding activity. Acts upstream of or within negative regulation of transmembrane transport; negative regulation of transporter activity; and protein dephosphorylation. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CTTNBP2NL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CTTNBP2NL	NM_018704.3 link	c.330+68G>T	intron_variant	Intron 4 of 5	ENST00000271277.11	NP_061174.1	Q9P2B4
CTTNBP2NL	XM_011541781.3 link	c.330+68G>T	intron_variant	Intron 4 of 5		XP_011540083.1	Q9P2B4
CTTNBP2NL	XM_017001806.2 link	c.330+68G>T	intron_variant	Intron 4 of 5		XP_016857295.1	Q9P2B4
CTTNBP2NL	XM_047425362.1 link	c.330+68G>T	intron_variant	Intron 4 of 5		XP_047281318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTTNBP2NL	ENST00000271277.11 link	c.330+68G>T		intron_variant	Intron 4 of 5	1	NM_018704.3	ENSP00000271277.6		Q9P2B4
CTTNBP2NL	ENST00000441739.1 link	c.330+68G>T		intron_variant	Intron 4 of 5	3		ENSP00000390976.1		B1AMN7

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31735

AN:

151308

Hom.:

4092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.239

AC:

177179

AN:

740196

Hom.:

23296

AF XY:

0.238

AC XY:

89792

AN XY:

377776

show subpopulations

African (AFR)

AF:

0.103

AC:

1917

AN:

18698

American (AMR)

AF:

0.368

AC:

9304

AN:

25272

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

4246

AN:

17106

East Asian (EAS)

AF:

0.509

AC:

16898

AN:

33214

South Asian (SAS)

AF:

0.226

AC:

12151

AN:

53696

European-Finnish (FIN)

AF:

0.290

AC:

13290

AN:

45848

Middle Eastern (MID)

AF:

0.194

AC:

619

AN:

3190

European-Non Finnish (NFE)

AF:

0.217

AC:

110103

AN:

507468

Other (OTH)

AF:

0.242

AC:

8651

AN:

35704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

6737

13474

20211

26948

33685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2852

5704

8556

11408

14260

<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:

0.210

AC:

31738

AN:

151426

Hom.:

4092

Cov.:

AF XY:

0.220

AC XY:

16221

AN XY:

73882

show subpopulations

African (AFR)

AF:

0.106

AC:

4383

AN:

41418

American (AMR)

AF:

0.309

AC:

4685

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

885

AN:

3462

East Asian (EAS)

AF:

0.556

AC:

2849

AN:

5122

South Asian (SAS)

AF:

0.231

AC:

1100

AN:

4758

European-Finnish (FIN)

AF:

0.291

AC:

3009

AN:

10356

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14078

AN:

67856

Other (OTH)

AF:

0.223

AC:

469

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

1023

2047

3070

4094

5117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.211

Hom.:

4636

Bravo

AF:

0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.8

(source)

DANN

Benign

0.69

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over