rs7727912

Variant names:

• chr5-1318845-T-C
• rs7727912
• NM_030782.5:c.1533-392A>G

Variant summary

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

The NM_030782.5(CLPTM1L):​c.1533-392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,270 control chromosomes in the GnomAD database, including 450 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 0.065 (450 hom., cov: 32)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1L	NM_030782.5	c.1533-392A>G		intron_variant	Intron 16 of 16	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3	c.1530-392A>G		intron_variant	Intron 16 of 16		XP_011512446.1
CLPTM1L	XM_024446222.2	c.999-392A>G		intron_variant	Intron 14 of 14		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1533-392A>G		intron_variant	Intron 16 of 16	1	NM_030782.5	ENSP00000313854.5

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9844 AN: 152152 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0646 AC: 9838 AN: 152270 Hom.: 450 Cov.: 32 AF XY: 0.0637 AC XY: 4740 AN XY: 74440

African (AFR) AF: 0.0218 AC: 904 AN: 41548

American (AMR) AF: 0.0500 AC: 765 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4832

European-Finnish (FIN) AF: 0.0959 AC: 1017 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6380 AN: 68008

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0698 Hom.: 387

Bravo AF: 0.0593

Asia WGS AF: 0.0200 AC: 71 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	0.43
DANN	Benign	0.50
PhyloP100		-0.12
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: rs7727912; hg19: chr5-1318960;