rs1993205

Variant names:

• chr11-44876149-C-T
• rs1993205
• NM_130783.5:c.-11+15680C>T

Variant summary

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

The NM_130783.5(TSPAN18):​c.-11+15680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,008 control chromosomes in the GnomAD database, including 33,082 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 0.65 (33082 hom., cov: 31)
• Consequence: TSPAN18 NM_130783.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN18	NM_130783.5	c.-11+15680C>T		intron_variant	Intron 3 of 9	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7	c.-11+15680C>T		intron_variant	Intron 3 of 9	5	NM_130783.5	ENSP00000429993.2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99168 AN: 151890 Hom.: 33077 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.653 AC: 99205 AN: 152008 Hom.: 33082 Cov.: 31 AF XY: 0.658 AC XY: 48903 AN XY: 74292

African (AFR) AF: 0.517 AC: 21432 AN: 41446

American (AMR) AF: 0.760 AC: 11630 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2137 AN: 3464

East Asian (EAS) AF: 0.822 AC: 4239 AN: 5158

South Asian (SAS) AF: 0.716 AC: 3439 AN: 4802

European-Finnish (FIN) AF: 0.737 AC: 7793 AN: 10576

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46519 AN: 67948

Other (OTH) AF: 0.657 AC: 1388 AN: 2112

Alfa AF: 0.664 Hom.: 63777

Bravo AF: 0.647

Asia WGS AF: 0.744 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.40
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1993205; hg19: chr11-44897700;