5-1317705-A-G

Variant summary

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

The 5-1317705-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,082 control chromosomes in the GnomAD database, including 26,894 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 0.59 (26891 hom., cov: 33)
  • Exomes 𝑓: 0.61 (3 hom.)
• Consequence: CLPTM1L NM_030782.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1L	NM_030782.5			downstream_gene_variant		ENST00000320895.10
CLPTM1L	XM_011514144.3			downstream_gene_variant
CLPTM1L	XM_024446222.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10			downstream_gene_variant		1	NM_030782.5	P1
CLPTM1L	ENST00000507807.3			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89552 AN: 151946 Hom.: 26876 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.611 AC: 11 AN: 18 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 7 AN XY: 14

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.589 AC: 89615 AN: 152064 Hom.: 26891 Cov.: 33 AF XY: 0.596 AC XY: 44267 AN XY: 74306

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.608

Alfa AF: 0.582 Hom.: 6547

Bravo AF: 0.592

Asia WGS AF: 0.780 AC: 2709 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	0.71
Dann	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3816659; hg19: chr5-1317820;