rs11988036

Variant names:

• chr8-20282696-T-A
• rs11988036
• NM_021020.5:c.-135+21044A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-20282696-T-A
• chr8-20282696-T-C

Variant summary

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

The NM_021020.5(LZTS1):​c.-135+21044A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,078 control chromosomes in the GnomAD database, including 6,597 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 0.29 (6597 hom., cov: 32)
• Consequence: LZTS1 NM_021020.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 2 publications found

Genes affected

LZTS1 (HGNC:13861): (leucine zipper tumor suppressor 1) This gene encodes a tumor suppressor protein that is ubiquitously expressed in normal tissues. In uveal melanomas, expression of this protein is silenced in rapidly metastasizing and metastatic tumor cells but has normal expression in slowly metastasizing or nonmetastasizing tumor cells. This protein may have a role in cell-cycle control by interacting with the Cdk1/cyclinB1 complex. This gene is located on chromosomal region 8p22. Loss of heterozygosity (LOH) in the 8p arm is a common characteristic of many types of cancer. [provided by RefSeq, Nov 2009]

LZTS1-AS1 (HGNC:43630): (LZTS1 antisense RNA 1)

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 (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS1	NM_021020.5	c.-135+21044A>T		intron_variant	Intron 1 of 3	ENST00000381569.5	NP_066300.1
LZTS1-AS1	NR_047509.1	n.143-6513T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTS1	ENST00000381569.5	c.-135+21044A>T		intron_variant	Intron 1 of 3	5	NM_021020.5	ENSP00000370981.1
LZTS1-AS1	ENST00000523103.1	n.143-6513T>A		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43601 AN: 151960 Hom.: 6589 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.287 AC: 43643 AN: 152078 Hom.: 6597 Cov.: 32 AF XY: 0.288 AC XY: 21383 AN XY: 74324

African (AFR) AF: 0.231 AC: 9576 AN: 41476

American (AMR) AF: 0.327 AC: 5002 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3468

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5166

South Asian (SAS) AF: 0.181 AC: 873 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4015 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21147 AN: 67970

Other (OTH) AF: 0.269 AC: 570 AN: 2116

Alfa AF: 0.302 Hom.: 862

Bravo AF: 0.283

Asia WGS AF: 0.256 AC: 892 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	0.38
DANN	Benign	0.58
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11988036; hg19: chr8-20140207;