11-44838820-A-G

Variant names:

• chr11-44838820-A-G
• rs835780
• NM_130783.5:c.-152-21508A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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

ENSG00000296707 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130783.5. 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
	TSPAN18	NM_130783.5	MANE Select	c.-152-21508A>G		intron	N/A	NP_570139.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN18	ENST00000520358.7	TSL:5 MANE Select	c.-152-21508A>G		intron	N/A	ENSP00000429993.2
	TSPAN18	ENST00000340160.7	TSL:5	c.-152-21508A>G		intron	N/A	ENSP00000339820.3
	TSPAN18	ENST00000520999.6	TSL:5	c.-199-21508A>G		intron	N/A	ENSP00000427942.2

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

African (AFR) AF: 0.845 AC: 35100 AN: 41516

American (AMR) AF: 0.912 AC: 13958 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3122 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4833 AN: 5188

South Asian (SAS) AF: 0.795 AC: 3837 AN: 4824

European-Finnish (FIN) AF: 0.888 AC: 9408 AN: 10600

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60236 AN: 68010

Other (OTH) AF: 0.894 AC: 1888 AN: 2112

Alfa AF: 0.881 Hom.: 29771

Bravo AF: 0.881

Asia WGS AF: 0.847 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.76
PhyloP100		0.82
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: rs835780; hg19: chr11-44860371;