Variant 11-44919277-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_130783.5(TSPAN18):c.397G>A(p.Val133Ile) variant causes a missense change. The variant allele was found at a frequency of 0.363 in 1,613,394 control chromosomes in the GnomAD database, including 112,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 7998 hom., cov: 32)

Exomes 𝑓: 0.37 ( 104085 hom. )

Consequence

TSPAN18
NM_130783.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.73

Variant links:

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]

TSPAN18 links:

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]

TP53I11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.376007E-4).

BP6

Variant 11-44919277-G-A is Benign according to our data. Variant chr11-44919277-G-A is described in ClinVar as [Benign]. Clinvar id is 3059513.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN18	NM_130783.5 linkuse as main transcript	c.397G>A	p.Val133Ile	missense_variant	7/10	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7 linkuse as main transcript	c.397G>A	p.Val133Ile	missense_variant	7/10	5	NM_130783.5	ENSP00000429993	P1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44593

AN:

151990

Hom.:

8001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.375

AC:

94359

AN:

251362

Hom.:

19384

AF XY:

0.378

AC XY:

51332

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0836

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.594

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.370

AC:

541168

AN:

1461286

Hom.:

104085

Cov.:

AF XY:

0.372

AC XY:

270470

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.293

AC:

44588

AN:

152108

Hom.:

7998

Cov.:

AF XY:

0.299

AC XY:

22219

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.582

Gnomad4 SAS

AF:

0.473

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.344

Hom.:

23699

Bravo

AF:

0.285

TwinsUK

AF:

0.385

AC:

1428

ALSPAC

AF:

0.374

AC:

1440

ESP6500AA

AF:

0.0999

AC:

440

ESP6500EA

AF:

0.342

AC:

2937

ExAC

AF:

0.370

AC:

44901

Asia WGS

AF:

0.497

AC:

1726

AN:

3478

EpiCase

AF:

0.335

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TSPAN18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.098

.;T;T;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T;T;T;.

MetaRNN

Benign

0.00034

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

.;.;L;.;L

MutationTaster

Benign

0.00074

P;P

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.48

N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T

Polyphen

0.36

.;.;B;.;B

Vest4

0.053, 0.054

MPC

0.27

ClinPred

0.0042

GERP RS

2.4

Varity_R

0.073

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over