Genetic Variant NM_030782.5: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5 link	c.976+695T>C	intron_variant	Intron 8 of 16	ENST00000320895.10	NP_110409.2	Q96KA5-1
CLPTM1L	XM_011514144.3 link	c.973+695T>C	intron_variant	Intron 8 of 16		XP_011512446.1
CLPTM1L	XM_024446222.2 link	c.442+695T>C	intron_variant	Intron 6 of 14		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10 link	c.976+695T>C		intron_variant	Intron 8 of 16	1	NM_030782.5	ENSP00000313854.5		Q96KA5-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over