5-1332962-A-G

Variant names:

• chr5-1332962-A-G
• rs2447853
• NM_030782.5:c.892-1079T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030782.5(CLPTM1L):​c.892-1079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 147,574 control chromosomes in the GnomAD database, including 15,740 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 0.45 (15740 hom., cov: 28)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.892-1079T>C		intron_variant	Intron 7 of 16	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.889-1079T>C		intron_variant	Intron 7 of 16		XP_011512446.1
CLPTM1L	XM_024446222.2	c.358-1079T>C		intron_variant	Intron 5 of 14		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.892-1079T>C		intron_variant	Intron 7 of 16	1	NM_030782.5	ENSP00000313854.5

Frequencies

GnomAD3 genomes AF: 0.454 AC: 66905 AN: 147434 Hom.: 15730 Cov.: 28

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.454 AC: 66961 AN: 147574 Hom.: 15740 Cov.: 28 AF XY: 0.446 AC XY: 32074 AN XY: 71968

African (AFR) AF: 0.573 AC: 23048 AN: 40224

American (AMR) AF: 0.338 AC: 5022 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1524 AN: 3408

East Asian (EAS) AF: 0.190 AC: 900 AN: 4744

South Asian (SAS) AF: 0.222 AC: 993 AN: 4464

European-Finnish (FIN) AF: 0.476 AC: 4819 AN: 10128

Middle Eastern (MID) AF: 0.468 AC: 130 AN: 278

European-Non Finnish (NFE) AF: 0.439 AC: 29221 AN: 66540

Other (OTH) AF: 0.429 AC: 875 AN: 2040

Alfa AF: 0.573 Hom.: 4380

Bravo AF: 0.447

Asia WGS AF: 0.227 AC: 790 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.24
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2447853; hg19: chr5-1333077;