NM_030782.5:c.1371+6G>A

Variant names:

• chr5-1321758-C-T
• rs10073340
• NM_030782.5:c.1371+6G>A

Variant summary

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

The NM_030782.5(CLPTM1L):​c.1371+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,820 control chromosomes in the GnomAD database, including 22,317 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2102 hom., cov: 34)
  • Exomes 𝑓: 0.16 (20215 hom.)
• Consequence: CLPTM1L NM_030782.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006546
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 21 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	NM_030782.5	MANE Select	c.1371+6G>A		splice_region intron	N/A	NP_110409.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	ENST00000320895.10	TSL:1 MANE Select	c.1371+6G>A		splice_region intron	N/A	ENSP00000313854.5
	CLPTM1L	ENST00000507807.3	TSL:1	c.864+6G>A		splice_region intron	N/A	ENSP00000423321.1
	CLPTM1L	ENST00000505605.5	TSL:2	n.275G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24594 AN: 152080 Hom.: 2100 Cov.: 34

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.146 AC: 36586 AN: 251196 AF XY: 0.144

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0808

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0557

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.161 AC: 235929 AN: 1461622 Hom.: 20215 Cov.: 36 AF XY: 0.159 AC XY: 115322 AN XY: 727122

African (AFR) AF: 0.154 AC: 5150 AN: 33476

American (AMR) AF: 0.0866 AC: 3871 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5414 AN: 26136

East Asian (EAS) AF: 0.0456 AC: 1810 AN: 39700

South Asian (SAS) AF: 0.0724 AC: 6242 AN: 86252

European-Finnish (FIN) AF: 0.227 AC: 12096 AN: 53318

Middle Eastern (MID) AF: 0.177 AC: 1022 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 190745 AN: 1111858

Other (OTH) AF: 0.159 AC: 9579 AN: 60390

GnomAD4 genome AF: 0.162 AC: 24611 AN: 152198 Hom.: 2102 Cov.: 34 AF XY: 0.161 AC XY: 12014 AN XY: 74416

African (AFR) AF: 0.154 AC: 6378 AN: 41534

American (AMR) AF: 0.132 AC: 2021 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.0504 AC: 261 AN: 5174

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4828

European-Finnish (FIN) AF: 0.228 AC: 2410 AN: 10590

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11823 AN: 67986

Other (OTH) AF: 0.161 AC: 341 AN: 2114

Alfa AF: 0.167 Hom.: 4411

Bravo AF: 0.154

Asia WGS AF: 0.0750 AC: 261 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs10073340; hg19: chr5-1321873;