chr5-1342599-C-A

Variant names:

• chr5-1342599-C-A
• rs31489
• NM_030782.5:c.264-739G>T

Variant summary

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

The NM_030782.5(CLPTM1L):​c.264-739G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,072 control chromosomes in the GnomAD database, including 13,051 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 0.41 (13051 hom., cov: 33)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 94 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.264-739G>T		intron_variant	Intron 2 of 16	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.264-739G>T		intron_variant	Intron 2 of 16		XP_011512446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.264-739G>T		intron_variant	Intron 2 of 16	1	NM_030782.5	ENSP00000313854.5
CLPTM1L	ENST00000630539.1	c.-136-739G>T		intron_variant	Intron 2 of 15	5		ENSP00000485923.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61733 AN: 151954 Hom.: 13040 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.406 AC: 61789 AN: 152072 Hom.: 13051 Cov.: 33 AF XY: 0.400 AC XY: 29737 AN XY: 74336

African (AFR) AF: 0.484 AC: 20070 AN: 41468

American (AMR) AF: 0.308 AC: 4711 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3468

East Asian (EAS) AF: 0.179 AC: 925 AN: 5166

South Asian (SAS) AF: 0.194 AC: 933 AN: 4816

European-Finnish (FIN) AF: 0.443 AC: 4679 AN: 10570

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27671 AN: 67994

Other (OTH) AF: 0.395 AC: 833 AN: 2110

Alfa AF: 0.401 Hom.: 53140

Bravo AF: 0.403

Asia WGS AF: 0.216 AC: 753 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	1.4
DANN	Benign	0.64
PhyloP100		-0.93
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: rs31489; hg19: chr5-1342714;