11-44838820-A-G

Variant summary

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

The NM_130783.5(TSPAN18):c.-152-21508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,224 control chromosomes in the GnomAD database, including 58,537 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 0.88 (58537 hom., cov: 32)
• Consequence: TSPAN18 NM_130783.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN18	NM_130783.5	c.-152-21508A>G		intron_variant		ENST00000520358.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN18	ENST00000520358.7	c.-152-21508A>G		intron_variant		5	NM_130783.5	P1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133299 AN: 152106 Hom.: 58477 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.876 AC: 133419 AN: 152224 Hom.: 58537 Cov.: 32 AF XY: 0.875 AC XY: 65168 AN XY: 74436

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.894

Alfa AF: 0.881 Hom.: 26441

Bravo AF: 0.881

Asia WGS AF: 0.847 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.5
Dann	Benign	0.76

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: rs835780; hg19: chr11-44860371;