rs10073340

Positions:

• chr5-1321758-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.1371+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,820 control chromosomes in the GnomAD database, including 22,317 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 0.16 (2102 hom., cov: 34)
  • Exomes 𝑓: 0.16 (20215 hom.)
• Consequence: CLPTM1L NM_030782.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00006546
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1L	NM_030782.5	c.1371+6G>A		splice_donor_region_variant, intron_variant		ENST00000320895.10
CLPTM1L	XM_011514144.3	c.1368+6G>A		splice_donor_region_variant, intron_variant
CLPTM1L	XM_024446222.2	c.837+6G>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1371+6G>A		splice_donor_region_variant, intron_variant		1	NM_030782.5	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24594 AN: 152080 Hom.: 2100 Cov.: 34

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.161

GnomAD3 exomes AF: 0.146 AC: 36586 AN: 251196 Hom.: 3145 AF XY: 0.144 AC XY: 19562 AN XY: 135796

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0808

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0557

Gnomad SAS exome AF: 0.0719

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.161 AC: 235929 AN: 1461622 Hom.: 20215 Cov.: 36 AF XY: 0.159 AC XY: 115322 AN XY: 727122

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0866

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0456

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.162 AC: 24611 AN: 152198 Hom.: 2102 Cov.: 34 AF XY: 0.161 AC XY: 12014 AN XY: 74416

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0504

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.161

Alfa AF: 0.168 Hom.: 3700

Bravo AF: 0.154

Asia WGS AF: 0.0750 AC: 261 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs10073340; hg19: chr5-1321873;