Variant 19-44955086-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PVS1_ModerateBP6BS2

The NM_001282175.2(CLPTM1):c.30+1G>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,535,742 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

CLPTM1
NM_001282175.2 splice_donor, intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

CLPTM1 (HGNC:):

CLPTM1 links:

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLPTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.046747968 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 19-44955086-G-T is Benign according to our data. Variant chr19-44955086-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038555.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 376 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1	NM_001282175.2 linkuse as main transcript	c.30+1G>T		splice_donor_variant, intron_variant			NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2 linkuse as main transcript	c.-235+385G>T		intron_variant			NP_001269105.1	O96005-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
CLPTM1	ENST00000588855.5 linkuse as main transcript	n.117+385G>T	intron_variant	1
CLPTM1	ENST00000541297.6 linkuse as main transcript	c.30+1G>T	splice_donor_variant, intron_variant	2	ENSP00000442011.1	O96005-4
CLPTM1	ENST00000546079.5 linkuse as main transcript	c.-235+385G>T	intron_variant	2	ENSP00000443192.1	O96005-3

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000436

AC:

AN:

128436

Hom.:

AF XY:

0.000355

AC XY:

AN XY:

70332

show subpopulations

Gnomad AFR exome

AF:

0.00854

Gnomad AMR exome

AF:

0.0000821

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000447

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000226

AC:

312

AN:

1383390

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

137

AN XY:

682586

show subpopulations

Gnomad4 AFR exome

AF:

0.00867

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.000294

GnomAD4 genome

AF:

0.00247

AC:

376

AN:

152352

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00873

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000333

Hom.:

Bravo

AF:

0.00263

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLPTM1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.22

DANN

Benign

0.55

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.022

GERP RS

-4.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over