rs428499

Variant names:

• chr5-1322548-T-C
• rs428499
• NM_030782.5:c.1315+329A>G

Variant summary

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

The NM_030782.5(CLPTM1L):​c.1315+329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,274 control chromosomes in the GnomAD database, including 48,492 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 0.80 (48492 hom., cov: 35)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1315+329A>G		intron_variant	Intron 13 of 16	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1312+329A>G		intron_variant	Intron 13 of 16		XP_011512446.1
CLPTM1L	XM_024446222.2	c.781+329A>G		intron_variant	Intron 11 of 14		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1315+329A>G		intron_variant	Intron 13 of 16	1	NM_030782.5	ENSP00000313854.5

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121349 AN: 152154 Hom.: 48465 Cov.: 35

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.797 AC: 121432 AN: 152274 Hom.: 48492 Cov.: 35 AF XY: 0.796 AC XY: 59239 AN XY: 74458

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.782

Alfa AF: 0.805 Hom.: 15780

Bravo AF: 0.796

Asia WGS AF: 0.697 AC: 2424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.27

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: rs428499; hg19: chr5-1322663;