5-1344343-G-A

Position:

• chr5-1344343-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.263+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,584,154 control chromosomes in the GnomAD database, including 137,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14146 hom., cov: 34)
  • Exomes 𝑓: 0.41 (123064 hom.)
• Consequence: CLPTM1L NM_030782.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004899
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.263+8C>T		splice_region_variant, intron_variant		ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.263+8C>T		splice_region_variant, intron_variant			XP_011512446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.263+8C>T		splice_region_variant, intron_variant		1	NM_030782.5	ENSP00000313854.5
CLPTM1L	ENST00000630539.1	c.-137+8C>T		splice_region_variant, intron_variant		5		ENSP00000485923.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64240 AN: 152016 Hom.: 14134 Cov.: 34

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.409

GnomAD3 exomes AF: 0.365 AC: 91153 AN: 249710 Hom.: 18308 AF XY: 0.364 AC XY: 49145 AN XY: 135158

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.406 AC: 581061 AN: 1432022 Hom.: 123064 Cov.: 27 AF XY: 0.400 AC XY: 285741 AN XY: 714068

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.423 AC: 64294 AN: 152132 Hom.: 14146 Cov.: 34 AF XY: 0.416 AC XY: 30970 AN XY: 74370

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.407

Alfa AF: 0.431 Hom.: 19970

Bravo AF: 0.418

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0020
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: rs31490; hg19: chr5-1344458;