rs401681

Positions:

• chr5-1321972-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.1316-153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 704,354 control chromosomes in the GnomAD database, including 67,106 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 0.47 (17548 hom., cov: 34)
  • Exomes 𝑓: 0.41 (49558 hom.)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1316-153G>A		intron_variant		ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1313-153G>A		intron_variant			XP_011512446.1
CLPTM1L	XM_024446222.2	c.782-153G>A		intron_variant			XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1316-153G>A		intron_variant		1	NM_030782.5	ENSP00000313854	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71708 AN: 151958 Hom.: 17526 Cov.: 34

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.414 AC: 228381 AN: 552278 Hom.: 49558 AF XY: 0.402 AC XY: 117952 AN XY: 293754

Gnomad4 AFR exome AF: 0.593

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.472 AC: 71787 AN: 152076 Hom.: 17548 Cov.: 34 AF XY: 0.467 AC XY: 34746 AN XY: 74354

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.451

Alfa AF: 0.433 Hom.: 17929

Bravo AF: 0.480

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.39

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: rs401681; hg19: chr5-1322087; COSMIC: COSV57990702; COSMIC: COSV57990702;