Genetic Variant CLPTM1L:c.*664T>C (chr5-1317705-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.*664T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,082 control chromosomes in the GnomAD database, including 26,894 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 0.59 ( 26891 hom., cov: 33)

Exomes 𝑓: 0.61 ( 3 hom. )

Consequence

CLPTM1L
NM_030782.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CLPTM1L	NM_030782.5 link	c.*664T>C	downstream_gene_variant	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3 link	c.*664T>C	downstream_gene_variant		XP_011512446.1
CLPTM1L	XM_024446222.2 link	c.*664T>C	downstream_gene_variant		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
CLPTM1L	ENST00000320895.10 link	c.*664T>C	downstream_gene_variant	1	NM_030782.5	ENSP00000313854.5
CLPTM1L	ENST00000507807.3 link	c.*664T>C	downstream_gene_variant	1		ENSP00000423321.1
CLPTM1L	ENST00000630539.1 link	c.*664T>C	downstream_gene_variant	5		ENSP00000485923.1
CLPTM1L	ENST00000503042.5 link	n.*163T>C	downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89552

AN:

151946

Hom.:

26876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.606

GnomAD4 exome

AF:

0.611

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

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:

0.589

AC:

89615

AN:

152064

Hom.:

26891

Cov.:

AF XY:

0.596

AC XY:

44267

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.512

AC:

21247

AN:

41468

American (AMR)

AF:

0.691

AC:

10561

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2048

AN:

3468

East Asian (EAS)

AF:

0.818

AC:

4222

AN:

5162

South Asian (SAS)

AF:

0.806

AC:

3886

AN:

4822

European-Finnish (FIN)

AF:

0.553

AC:

5831

AN:

10544

Middle Eastern (MID)

AF:

0.575

AC:

168

AN:

292

European-Non Finnish (NFE)

AF:

0.587

AC:

39890

AN:

67996

Other (OTH)

AF:

0.608

AC:

1284

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1886

3772

5657

7543

9429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.582

Hom.:

11812

Bravo

AF:

0.592

Asia WGS

AF:

0.780

AC:

2709

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.71

(source)

DANN

Benign

0.47

PhyloP100

-2.3

Mutation Taster

=94/6

polymorphism

(source)

Splicing

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