rs421629

Positions:

• chr5-1320021-G-A
• chr5-1320021-G-C

Variant summary

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

The NM_030782.5(CLPTM1L):​c.1532+595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,062 control chromosomes in the GnomAD database, including 19,909 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 0.49 (19909 hom., cov: 34)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1532+595C>T		intron_variant		ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1529+595C>T		intron_variant			XP_011512446.1
CLPTM1L	XM_024446222.2	c.998+595C>T		intron_variant			XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1532+595C>T		intron_variant		1	NM_030782.5	ENSP00000313854	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74122 AN: 151944 Hom.: 19882 Cov.: 34

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.488 AC: 74204 AN: 152062 Hom.: 19909 Cov.: 34 AF XY: 0.479 AC XY: 35624 AN XY: 74320

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.455

Alfa AF: 0.407 Hom.: 2745

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.67

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: rs421629; hg19: chr5-1320136;