5-1331104-A-G

Position:

• chr5-1331104-A-G

Variant summary

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

The NM_030782.5(CLPTM1L):​c.976+695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,610 control chromosomes in the GnomAD database, including 16,244 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 (16179 hom., cov: 33)
  • Exomes 𝑓: 0.40 (65 hom.)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.976+695T>C		intron_variant		ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.973+695T>C		intron_variant			XP_011512446.1
CLPTM1L	XM_024446222.2	c.442+695T>C		intron_variant			XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.976+695T>C		intron_variant		1	NM_030782.5	ENSP00000313854	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68315 AN: 151716 Hom.: 16166 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.405 AC: 315 AN: 778 Hom.: 65 Cov.: 0 AF XY: 0.421 AC XY: 202 AN XY: 480

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.450 AC: 68379 AN: 151832 Hom.: 16179 Cov.: 33 AF XY: 0.443 AC XY: 32847 AN XY: 74202

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.427

Alfa AF: 0.435 Hom.: 1815

Bravo AF: 0.448

Asia WGS AF: 0.232 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.72
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4

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: rs370348; hg19: chr5-1331219;