rs7257610

Positions:

• chr19-44987170-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.794-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,604,814 control chromosomes in the GnomAD database, including 2,193 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 0.064 (386 hom., cov: 34)
  • Exomes 𝑓: 0.046 (1807 hom.)
• Consequence: CLPTM1 NM_001294.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003402
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1	NM_001294.4	c.794-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000337392.10	NP_001285.1
CLPTM1	NM_001282175.2	c.752-9G>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001269104.1
CLPTM1	NM_001282176.2	c.488-9G>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001269105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1	ENST00000337392.10	c.794-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001294.4	ENSP00000336994	P1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9728 AN: 152166 Hom.: 385 Cov.: 34

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0569

GnomAD3 exomes AF: 0.0487 AC: 12062 AN: 247882 Hom.: 370 AF XY: 0.0499 AC XY: 6688 AN XY: 133936

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.0534

Gnomad EAS exome AF: 0.0229

Gnomad SAS exome AF: 0.0711

Gnomad FIN exome AF: 0.0379

Gnomad NFE exome AF: 0.0459

Gnomad OTH exome AF: 0.0491

GnomAD4 exome AF: 0.0462 AC: 67067 AN: 1452530 Hom.: 1807 Cov.: 30 AF XY: 0.0471 AC XY: 33939 AN XY: 721096

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.0543

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.0361

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.0497

GnomAD4 genome AF: 0.0640 AC: 9741 AN: 152284 Hom.: 386 Cov.: 34 AF XY: 0.0630 AC XY: 4692 AN XY: 74470

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0510 Hom.: 298

Bravo AF: 0.0650

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.036
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: rs7257610; hg19: chr19-45490428; COSMIC: COSV61612846; COSMIC: COSV61612846;