Genetic Variant CLPTM1:c.794-9G>A (chr19-44987170-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001294.4(CLPTM1):c.794-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,604,814 control chromosomes in the GnomAD database, including 2,193 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 0.064 ( 386 hom., cov: 34)

Exomes 𝑓: 0.046 ( 1807 hom. )

Consequence

CLPTM1
NM_001294.4 intron

Scores

Splicing: ADA: 0.0003402

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

12 publications found

Variant links:

Genes affected

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLPTM1 links:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLPTM1	NM_001294.4	MANE Select	c.794-9G>A	intron	N/A	NP_001285.1	A0A0S2Z3H2
CLPTM1	NM_001282175.2		c.752-9G>A	intron	N/A	NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2		c.488-9G>A	intron	N/A	NP_001269105.1	O96005-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.794-9G>A	intron	N/A	ENSP00000336994.4	O96005-1
CLPTM1	ENST00000588855.5	TSL:1	n.839-9G>A	intron	N/A
CLPTM1	ENST00000870268.1		c.794-9G>A	intron	N/A	ENSP00000540327.1

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9728

AN:

152166

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.0859

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0569

GnomAD2 exomes

AF:

0.0487

AC:

12062

AN:

247882

AF XY:

0.0499

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0534

Gnomad EAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.0379

Gnomad NFE exome

AF:

0.0459

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0462

AC:

67067

AN:

1452530

Hom.:

1807

Cov.:

AF XY:

0.0471

AC XY:

33939

AN XY:

721096

show subpopulations

African (AFR)

AF:

0.118

AC:

3920

AN:

33282

American (AMR)

AF:

0.0261

AC:

1155

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.0543

AC:

1397

AN:

25726

East Asian (EAS)

AF:

0.0149

AC:

588

AN:

39538

South Asian (SAS)

AF:

0.0730

AC:

6249

AN:

85588

European-Finnish (FIN)

AF:

0.0361

AC:

1920

AN:

53152

Middle Eastern (MID)

AF:

0.0591

AC:

339

AN:

5738

European-Non Finnish (NFE)

AF:

0.0439

AC:

48520

AN:

1105260

Other (OTH)

AF:

0.0497

AC:

2979

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3358

6716

10075

13433

16791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1838

3676

5514

7352

9190

<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:

0.0640

AC:

9741

AN:

152284

Hom.:

386

Cov.:

AF XY:

0.0630

AC XY:

4692

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.114

AC:

4736

AN:

41536

American (AMR)

AF:

0.0387

AC:

592

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

179

AN:

3470

East Asian (EAS)

AF:

0.0235

AC:

122

AN:

5184

South Asian (SAS)

AF:

0.0857

AC:

414

AN:

4828

European-Finnish (FIN)

AF:

0.0403

AC:

428

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0444

AC:

3018

AN:

68024

Other (OTH)

AF:

0.0563

AC:

119

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

474

948

1421

1895

2369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0522

Hom.:

397

Bravo

AF:

0.0650

Asia WGS

AF:

0.0400

AC:

142

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.14

(source)

DANN

Benign

0.81

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

dbscSNV1_RF

Benign

0.036

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over