rs414965

chr5-1324006-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030782.5(CLPTM1L):c.1198-137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 683,080 control chromosomes in the GnomAD database, including 51,471 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 0.41 (13174 hom., cov: 33)
  • Exomes 𝑓: 0.37 (38297 hom.)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1L	NM_030782.5	c.1198-137C>T		intron_variant		ENST00000320895.10
CLPTM1L	XM_011514144.3	c.1195-137C>T		intron_variant
CLPTM1L	XM_024446222.2	c.664-137C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1198-137C>T		intron_variant		1	NM_030782.5	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62038 AN: 151912 Hom.: 13163 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.366 AC: 194577 AN: 531050 Hom.: 38297 Cov.: 6 AF XY: 0.357 AC XY: 100674 AN XY: 281652

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.408 AC: 62094 AN: 152030 Hom.: 13174 Cov.: 33 AF XY: 0.402 AC XY: 29881 AN XY: 74276

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.393

Alfa AF: 0.413 Hom.: 2151

Bravo AF: 0.405

Asia WGS AF: 0.219 AC: 767 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	4.5
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

LitVar

Other links and lift over

dbSNP: rs414965; hg19: chr5-1324121;