rs16979595

Positions:

• chr19-44974124-G-A

Variant summary

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

The NM_001294.4(CLPTM1):​c.310-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,734 control chromosomes in the GnomAD database, including 2,922 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 0.19 (2922 hom., cov: 31)
• Consequence: CLPTM1 NM_001294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1	NM_001294.4	c.310-315G>A		intron_variant		ENST00000337392.10
CLPTM1	NM_001282175.2	c.268-315G>A		intron_variant
CLPTM1	NM_001282176.2	c.4-315G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1	ENST00000337392.10	c.310-315G>A		intron_variant		1	NM_001294.4	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28879 AN: 151616 Hom.: 2923 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0553

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.190 AC: 28900 AN: 151734 Hom.: 2922 Cov.: 31 AF XY: 0.192 AC XY: 14229 AN XY: 74166

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.190

Alfa AF: 0.174 Hom.: 4311

Bravo AF: 0.193

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.8
DANN	Benign	0.44

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: rs16979595; hg19: chr19-45477381;