Genetic Variant NM_030782.5:c.1532+9G>A (chr5-1320607-C-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_030782.5(CLPTM1L):c.1532+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,495,778 control chromosomes in the GnomAD database, including 90,073 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 0.37 ( 11053 hom., cov: 34)

Exomes 𝑓: 0.34 ( 79020 hom. )

Consequence

CLPTM1L
NM_030782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.768

Publications

139 publications found

Variant links:

Genes affected

CLPTM1L (HGNC:24308): (CLPTM1 like) The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers. [provided by RefSeq, Nov 2015]

CLPTM1L 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	NM_030782.5	MANE Select	c.1532+9G>A		intron	N/A	NP_110409.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLPTM1L	ENST00000320895.10	TSL:1 MANE Select	c.1532+9G>A	intron	N/A	ENSP00000313854.5
CLPTM1L	ENST00000507807.3	TSL:1	c.1025+9G>A	intron	N/A	ENSP00000423321.1
CLPTM1L	ENST00000966757.1		c.1736+9G>A	intron	N/A	ENSP00000636816.1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56977

AN:

152068

Hom.:

11036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.327

AC:

46793

AN:

143060

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.396

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.338

AC:

454629

AN:

1343592

Hom.:

79020

Cov.:

AF XY:

0.332

AC XY:

219010

AN XY:

659214

show subpopulations

African (AFR)

AF:

0.479

AC:

14372

AN:

29996

American (AMR)

AF:

0.331

AC:

10749

AN:

32484

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7161

AN:

24248

East Asian (EAS)

AF:

0.328

AC:

11193

AN:

34154

South Asian (SAS)

AF:

0.172

AC:

13084

AN:

75950

European-Finnish (FIN)

AF:

0.399

AC:

19259

AN:

48272

Middle Eastern (MID)

AF:

0.284

AC:

1138

AN:

4014

European-Non Finnish (NFE)

AF:

0.346

AC:

358960

AN:

1038820

Other (OTH)

AF:

0.336

AC:

18713

AN:

55654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14136

28272

42409

56545

70681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11740

23480

35220

46960

58700

<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:

0.375

AC:

57043

AN:

152186

Hom.:

11053

Cov.:

AF XY:

0.373

AC XY:

27729

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.472

AC:

19598

AN:

41522

American (AMR)

AF:

0.335

AC:

5123

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1053

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1632

AN:

5170

South Asian (SAS)

AF:

0.177

AC:

855

AN:

4822

European-Finnish (FIN)

AF:

0.411

AC:

4349

AN:

10588

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23277

AN:

67994

Other (OTH)

AF:

0.359

AC:

758

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1874

3748

5621

7495

9369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.350

Hom.:

46278

Bravo

AF:

0.379

Asia WGS

AF:

0.256

AC:

893

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

(source)

DANN

Benign

0.62

PhyloP100

-0.77

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

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