NM_004690.4:c.-141+5953A>G

Variant names:

• chr6-149711896-T-C
• rs1934534
• NM_004690.4:c.-141+5953A>G

Variant summary

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

The NM_004690.4(LATS1):​c.-141+5953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,930 control chromosomes in the GnomAD database, including 17,586 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 0.46 (17586 hom., cov: 32)
• Consequence: LATS1 NM_004690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 13 publications found

Genes affected

LATS1 (HGNC:6514): (large tumor suppressor kinase 1) The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. [provided by RefSeq, Apr 2017]

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 = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LATS1	NM_004690.4	c.-141+5953A>G		intron_variant	Intron 1 of 7	ENST00000543571.6	NP_004681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LATS1	ENST00000543571.6	c.-141+5953A>G		intron_variant	Intron 1 of 7	1	NM_004690.4	ENSP00000437550.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70233 AN: 151814 Hom.: 17553 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.463 AC: 70313 AN: 151930 Hom.: 17586 Cov.: 32 AF XY: 0.467 AC XY: 34714 AN XY: 74278

African (AFR) AF: 0.586 AC: 24264 AN: 41392

American (AMR) AF: 0.574 AC: 8745 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4165 AN: 5136

South Asian (SAS) AF: 0.412 AC: 1981 AN: 4812

European-Finnish (FIN) AF: 0.379 AC: 4010 AN: 10586

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24266 AN: 67964

Other (OTH) AF: 0.468 AC: 991 AN: 2116

Alfa AF: 0.394 Hom.: 6865

Bravo AF: 0.490

Asia WGS AF: 0.589 AC: 2049 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	0.11
DANN	Benign	0.58
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1934534; hg19: chr6-150033032;