11-44919322-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130783.5(TSPAN18):c.432+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,607,982 control chromosomes in the GnomAD database, including 15,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2071 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13291 hom.)
• Consequence: TSPAN18 NM_130783.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

Genes affected

TSPAN18 (HGNC:20660): (tetraspanin 18) Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TP53I11 (HGNC:16842): (tumor protein p53 inducible protein 11) Predicted to be involved in negative regulation of cell population proliferation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-44919322-G-A is Benign according to our data. Variant chr11-44919322-G-A is described in ClinVar as [Benign]. Clinvar id is 3057047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN18	NM_130783.5	c.432+10G>A		intron_variant		ENST00000520358.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN18	ENST00000520358.7	c.432+10G>A		intron_variant		5	NM_130783.5	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23982 AN: 151978 Hom.: 2068 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.144 AC: 36054 AN: 250960 Hom.: 2987 AF XY: 0.142 AC XY: 19232 AN XY: 135662

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.0361

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.131 AC: 190190 AN: 1455886 Hom.: 13291 Cov.: 30 AF XY: 0.131 AC XY: 95075 AN XY: 724650

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0437

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.158 AC: 24002 AN: 152096 Hom.: 2071 Cov.: 33 AF XY: 0.158 AC XY: 11709 AN XY: 74324

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0449

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.141

Alfa AF: 0.135 Hom.: 1631

Bravo AF: 0.156

Asia WGS AF: 0.106 AC: 370 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.120

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TSPAN18-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.7
Dann	Benign	0.77

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: rs11038214; hg19: chr11-44940873; COSMIC: COSV60882105; COSMIC: COSV60882105;