rs414965

Variant names:

• chr5-1324006-G-A
• rs414965
• NM_030782.5:c.1198-137C>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.1198-137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 683,080 control chromosomes in the GnomAD database, including 51,471 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 (13174 hom., cov: 33)
  • Exomes 𝑓: 0.37 (38297 hom.)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1198-137C>T		intron_variant	Intron 11 of 16	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1195-137C>T		intron_variant	Intron 11 of 16		XP_011512446.1
CLPTM1L	XM_024446222.2	c.664-137C>T		intron_variant	Intron 9 of 14		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1198-137C>T		intron_variant	Intron 11 of 16	1	NM_030782.5	ENSP00000313854.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62038 AN: 151912 Hom.: 13163 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.366 AC: 194577 AN: 531050 Hom.: 38297 Cov.: 6 AF XY: 0.357 AC XY: 100674 AN XY: 281652

African (AFR) AF: 0.489 AC: 7252 AN: 14830

American (AMR) AF: 0.225 AC: 6594 AN: 29274

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 6518 AN: 16762

East Asian (EAS) AF: 0.157 AC: 4991 AN: 31706

South Asian (SAS) AF: 0.196 AC: 10620 AN: 54266

European-Finnish (FIN) AF: 0.448 AC: 15334 AN: 34264

Middle Eastern (MID) AF: 0.361 AC: 836 AN: 2318

European-Non Finnish (NFE) AF: 0.412 AC: 131140 AN: 318464

Other (OTH) AF: 0.387 AC: 11292 AN: 29166

GnomAD4 genome AF: 0.408 AC: 62094 AN: 152030 Hom.: 13174 Cov.: 33 AF XY: 0.402 AC XY: 29881 AN XY: 74276

African (AFR) AF: 0.486 AC: 20161 AN: 41468

American (AMR) AF: 0.311 AC: 4753 AN: 15282

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

East Asian (EAS) AF: 0.181 AC: 928 AN: 5140

South Asian (SAS) AF: 0.196 AC: 944 AN: 4828

European-Finnish (FIN) AF: 0.446 AC: 4719 AN: 10572

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

European-Non Finnish (NFE) AF: 0.409 AC: 27794 AN: 67958

Other (OTH) AF: 0.393 AC: 829 AN: 2110

Alfa AF: 0.415 Hom.: 2235

Bravo AF: 0.405

Asia WGS AF: 0.219 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs414965; hg19: chr5-1324121;