19-44979627-T-C

Variant names:

• chr19-44979627-T-C
• rs7257916
• NM_001294.4:c.586+2167T>C

Variant summary

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

The NM_001294.4(CLPTM1):​c.586+2167T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,002 control chromosomes in the GnomAD database, including 13,468 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 0.40 (13468 hom., cov: 31)
• Consequence: CLPTM1 NM_001294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 20 publications found

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

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 = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294.4. 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
	CLPTM1	NM_001294.4	MANE Select	c.586+2167T>C		intron	N/A	NP_001285.1
	CLPTM1	NM_001282175.2		c.544+2167T>C		intron	N/A	NP_001269104.1
	CLPTM1	NM_001282176.2		c.280+2167T>C		intron	N/A	NP_001269105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.586+2167T>C		intron	N/A	ENSP00000336994.4
	CLPTM1	ENST00000588855.5	TSL:1	n.631+2167T>C		intron	N/A
	CLPTM1	ENST00000541297.6	TSL:2	c.544+2167T>C		intron	N/A	ENSP00000442011.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60632 AN: 151884 Hom.: 13463 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.399 AC: 60645 AN: 152002 Hom.: 13468 Cov.: 31 AF XY: 0.397 AC XY: 29482 AN XY: 74296

African (AFR) AF: 0.225 AC: 9347 AN: 41494

American (AMR) AF: 0.326 AC: 4973 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1896 AN: 5142

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 4996 AN: 10546

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34307 AN: 67956

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.477 Hom.: 18404

Bravo AF: 0.380

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		0.43
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: rs7257916; hg19: chr19-45482884;