rs402710

Positions:

• chr5-1320607-C-T

Variant summary

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

The NM_030782.5(CLPTM1L):​c.1532+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,495,778 control chromosomes in the GnomAD database, including 90,073 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 0.37 (11053 hom., cov: 34)
  • Exomes 𝑓: 0.34 (79020 hom.)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1532+9G>A		intron_variant		ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1529+9G>A		intron_variant			XP_011512446.1
CLPTM1L	XM_024446222.2	c.998+9G>A		intron_variant			XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1532+9G>A		intron_variant		1	NM_030782.5	ENSP00000313854	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56977 AN: 152068 Hom.: 11036 Cov.: 34

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.327 AC: 46793 AN: 143060 Hom.: 8048 AF XY: 0.315 AC XY: 23660 AN XY: 75200

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.328

GnomAD4 exome AF: 0.338 AC: 454629 AN: 1343592 Hom.: 79020 Cov.: 23 AF XY: 0.332 AC XY: 219010 AN XY: 659214

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.375 AC: 57043 AN: 152186 Hom.: 11053 Cov.: 34 AF XY: 0.373 AC XY: 27729 AN XY: 74402

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.359

Alfa AF: 0.343 Hom.: 22905

Bravo AF: 0.379

Asia WGS AF: 0.256 AC: 893 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs402710; hg19: chr5-1320722; COSMIC: COSV57990027; COSMIC: COSV57990027;