chr11-44862565-T-C

Variant names:

• chr11-44862565-T-C
• rs1966864
• NM_130783.5:c.-11+2096T>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.-11+2096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,098 control chromosomes in the GnomAD database, including 11,920 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 0.36 (11920 hom., cov: 32)
• Consequence: TSPAN18 NM_130783.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN18	NM_130783.5	c.-11+2096T>C		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+2096T>C		intron_variant	Intron 3 of 9	5	NM_130783.5	ENSP00000429993.2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55436 AN: 151980 Hom.: 11907 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.365 AC: 55479 AN: 152098 Hom.: 11920 Cov.: 32 AF XY: 0.361 AC XY: 26878 AN XY: 74370

African (AFR) AF: 0.597 AC: 24769 AN: 41482

American (AMR) AF: 0.315 AC: 4821 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1092 AN: 5148

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10588

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17984 AN: 67980

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.299 Hom.: 983

Bravo AF: 0.381

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		-0.58
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: rs1966864; hg19: chr11-44884116;