rs31490

Variant names:

• chr5-1344343-G-A
• rs31490
• NM_030782.5:c.263+8C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-1344343-G-A
• chr5-1344343-G-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.263+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,584,154 control chromosomes in the GnomAD database, including 137,210 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 0.42 (14146 hom., cov: 34)
  • Exomes 𝑓: 0.41 (123064 hom.)
• Consequence: CLPTM1L NM_030782.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004899
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 60 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 = 0.48 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.263+8C>T		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.263+8C>T		splice_region intron	N/A	ENSP00000313854.5
	CLPTM1L	ENST00000630539.1	TSL:5	c.-137+8C>T		splice_region intron	N/A	ENSP00000485923.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64240 AN: 152016 Hom.: 14134 Cov.: 34

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.365 AC: 91153 AN: 249710 AF XY: 0.364

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.406 AC: 581061 AN: 1432022 Hom.: 123064 Cov.: 27 AF XY: 0.400 AC XY: 285741 AN XY: 714068

African (AFR) AF: 0.490 AC: 16105 AN: 32838

American (AMR) AF: 0.223 AC: 9933 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 11126 AN: 25954

East Asian (EAS) AF: 0.161 AC: 6382 AN: 39572

South Asian (SAS) AF: 0.204 AC: 17479 AN: 85760

European-Finnish (FIN) AF: 0.473 AC: 25151 AN: 53154

Middle Eastern (MID) AF: 0.379 AC: 2175 AN: 5734

European-Non Finnish (NFE) AF: 0.432 AC: 468684 AN: 1084924

Other (OTH) AF: 0.404 AC: 24026 AN: 59450

GnomAD4 genome AF: 0.423 AC: 64294 AN: 152132 Hom.: 14146 Cov.: 34 AF XY: 0.416 AC XY: 30970 AN XY: 74370

African (AFR) AF: 0.485 AC: 20145 AN: 41504

American (AMR) AF: 0.323 AC: 4937 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.180 AC: 931 AN: 5180

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4826

European-Finnish (FIN) AF: 0.477 AC: 5039 AN: 10568

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29305 AN: 67970

Other (OTH) AF: 0.407 AC: 860 AN: 2114

Alfa AF: 0.426 Hom.: 45009

Bravo AF: 0.418

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.61
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0020
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: rs31490; hg19: chr5-1344458; COSMIC: COSV107348642; COSMIC: COSV107348642;