Genetic Variant CLPTM1L:c.976+695T>C (chr5-1331104-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.976+695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,610 control chromosomes in the GnomAD database, including 16,244 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 ( 16179 hom., cov: 33)

Exomes 𝑓: 0.40 ( 65 hom. )

Consequence

CLPTM1L
NM_030782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.736

Publications

18 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.976+695T>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.976+695T>C	intron	N/A	ENSP00000313854.5	Q96KA5-1
CLPTM1L	ENST00000507807.3	TSL:1	c.573+699T>C	intron	N/A	ENSP00000423321.1	G5E9Z2
CLPTM1L	ENST00000966757.1		c.976+695T>C	intron	N/A	ENSP00000636816.1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68315

AN:

151716

Hom.:

16166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.405

AC:

315

AN:

778

Hom.:

Cov.:

AF XY:

0.421

AC XY:

202

AN XY:

480

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.233

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.188

AC:

AN:

South Asian (SAS)

AF:

0.281

AC:

AN:

European-Finnish (FIN)

AF:

0.800

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.420

AC:

251

AN:

598

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.450

AC:

68379

AN:

151832

Hom.:

16179

Cov.:

AF XY:

0.443

AC XY:

32847

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.570

AC:

23597

AN:

41428

American (AMR)

AF:

0.333

AC:

5086

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1561

AN:

3468

East Asian (EAS)

AF:

0.182

AC:

938

AN:

5146

South Asian (SAS)

AF:

0.209

AC:

1000

AN:

4794

European-Finnish (FIN)

AF:

0.481

AC:

5067

AN:

10528

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29667

AN:

67892

Other (OTH)

AF:

0.427

AC:

898

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1935

3870

5804

7739

9674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.440

Hom.:

1934

Bravo

AF:

0.448

Asia WGS

AF:

0.232

AC:

811

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.72

PhyloP100

-0.74

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

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