Genetic Variant CLPTM1L:c.1146+63T>C (chr5-1325688-A-G) – 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.1146+63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,420,984 control chromosomes in the GnomAD database, including 130,989 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 0.45 ( 16331 hom., cov: 33)

Exomes 𝑓: 0.42 ( 114658 hom. )

Consequence

CLPTM1L
NM_030782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96

Publications

53 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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	NM_030782.5	MANE Select	c.1146+63T>C		intron	N/A	NP_110409.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLPTM1L	ENST00000320895.10	TSL:1 MANE Select	c.1146+63T>C	intron	N/A	ENSP00000313854.5	Q96KA5-1
CLPTM1L	ENST00000507807.3	TSL:1	c.639+63T>C	intron	N/A	ENSP00000423321.1	G5E9Z2
CLPTM1L	ENST00000966757.1		c.1146+63T>C	intron	N/A	ENSP00000636816.1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68588

AN:

151976

Hom.:

16313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.432

GnomAD4 exome

AF:

0.416

AC:

527652

AN:

1268890

Hom.:

114658

Cov.:

AF XY:

0.409

AC XY:

261422

AN XY:

639692

show subpopulations

African (AFR)

AF:

0.580

AC:

17129

AN:

29516

American (AMR)

AF:

0.229

AC:

9730

AN:

42568

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

10616

AN:

24102

East Asian (EAS)

AF:

0.170

AC:

6573

AN:

38650

South Asian (SAS)

AF:

0.205

AC:

16572

AN:

80854

European-Finnish (FIN)

AF:

0.478

AC:

25177

AN:

52684

Middle Eastern (MID)

AF:

0.388

AC:

2079

AN:

5360

European-Non Finnish (NFE)

AF:

0.443

AC:

417371

AN:

941352

Other (OTH)

AF:

0.416

AC:

22405

AN:

53804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14983

29967

44950

59934

74917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11776

23552

35328

47104

58880

<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:

0.451

AC:

68659

AN:

152094

Hom.:

16331

Cov.:

AF XY:

0.444

AC XY:

32995

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.575

AC:

23864

AN:

41490

American (AMR)

AF:

0.334

AC:

5112

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1560

AN:

3470

East Asian (EAS)

AF:

0.184

AC:

954

AN:

5180

South Asian (SAS)

AF:

0.208

AC:

1001

AN:

4816

European-Finnish (FIN)

AF:

0.480

AC:

5074

AN:

10570

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.436

AC:

29624

AN:

67974

Other (OTH)

AF:

0.430

AC:

907

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1882

3764

5645

7527

9409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.436

Hom.:

7669

Bravo

AF:

0.450

Asia WGS

AF:

0.236

AC:

823

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.35

(source)

DANN

Benign

0.41

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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