11-44834676-T-C

Variant names:

• chr11-44834676-T-C
• rs7124825
• NM_130783.5:c.-152-25652T>C

Variant summary

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

The NM_130783.5(TSPAN18):​c.-152-25652T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,010 control chromosomes in the GnomAD database, including 15,964 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 0.45 (15964 hom., cov: 32)
• Consequence: TSPAN18 NM_130783.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN18	NM_130783.5	c.-152-25652T>C		intron_variant	Intron 2 of 9	ENST00000520358.7	NP_570139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN18	ENST00000520358.7	c.-152-25652T>C		intron_variant	Intron 2 of 9	5	NM_130783.5	ENSP00000429993.2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68446 AN: 151892 Hom.: 15937 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.451 AC: 68514 AN: 152010 Hom.: 15964 Cov.: 32 AF XY: 0.452 AC XY: 33592 AN XY: 74262

African (AFR) AF: 0.482 AC: 19955 AN: 41430

American (AMR) AF: 0.525 AC: 8025 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4011 AN: 5158

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4818

European-Finnish (FIN) AF: 0.390 AC: 4125 AN: 10564

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28018 AN: 67978

Other (OTH) AF: 0.465 AC: 982 AN: 2114

Alfa AF: 0.432 Hom.: 55120

Bravo AF: 0.469

Asia WGS AF: 0.501 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.40
PhyloP100		-0.47
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: rs7124825; hg19: chr11-44856227; COSMIC: COSV60887897;